Radioactive-emission-measurement optimization to specific body structures

ABSTRACT

A method for predefining a set of radioactive-emission measurement views, for radioactive-emission imaging after an administration of a radiopharmaceutical, the method being tailored to a specific body structure and optimized with respect to the information gained about the body structure and based on modeling body-structure, based on its geometry and anatomical constraints, which limit accessibility to the body structure.

RELATED APPLICATIONS

This Application is a continuation of U.S. patent application Ser. No.11/607,075 filed on Dec. 1, 2006, which is a continuation-in-part of PCTPatent Application No. PCT/IL2005/000575 filed on Jun. 1, 2005, whichclaims the benefit of priority of U.S. Provisional Patent ApplicationNos. 60/648,690 filed on Feb. 2, 2005, 60/648,385 filed on Feb. 1, 2005,60/640,215 filed on Jan. 3, 2005, 60/636,088 filed on Dec. 16, 2004,60/635,630 filed on Dec. 14, 2004, 60/632,515 filed on Dec. 3, 2004,60/632,236 filed on Dec. 2, 2004, 60/630,561 filed on Nov. 26, 2004,60/625,971 filed on Nov. 9, 2004 and 60/575,369 filed on Jun. 1, 2004.

Ser. No. 11/607,075 is also a continuation-in-part of pending U.S.patent application Ser. No. 09/641,973 filed on Aug. 21, 2000.

Ser. No. 11/607,075 is also a continuation-in-part of pending U.S.patent application Ser. No. 10/343,792 filed on Feb. 4, 2003.

Ser. No. 11/607,075 is also a continuation-in-part of pending U.S.patent application Ser. No. 10/616,307 filed on Jul. 10, 2003.

Ser. No. 11/607,075 is also a continuation-in-part of U.S. patentapplication Ser. No. 10/533,568 filed on Jan. 5, 2006, now U.S. Pat. No.7,652,259.

All of the above Applications are incorporated herein by reference

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to nuclear imaging and more particularly,to systems, methods, and probes for radioactive-emission-measurementoptimization to specific body structures, possibly together withstructural imaging, for example, by x-rays, ultrasound, or MRI.

Radioactive-emission imaging relies on the fact that in general,pathologies, such as malignant tumors, malfunctioning organs, andinflammations, display a level of activity different from that ofhealthy tissue. Thus, radiopharmaceutical, which circulate in the bloodstream, are picked up by the active pathologies to a different extentthan by the surrounding healthy tissue; in consequence, the pathologiesare operative as radioactive-emission sources and may be detected byradioactive-emission imaging.

The pathological feature may appear as a concentrated source of highradiation, or a hot region, as may be associated with a tumor, or as aregion of low-level to radiation, which is nonetheless above thebackground level, as may be associated with carcinoma. Additionally, areversed situation is possible. Dead tissue has practically no pick upof radiopharmaceuticals, and is thus operative as a region of littleradiation, or a cold region, below the background level.

Thus radiopharmaceuticals may be used for identifying active pathologiesas well as dead tissue, and the image that is constructed is generallytermed, a functional image.

The mechanism of localization of a radiopharmaceutical in a particularorgan of interest depends on various processes in the organ of interest,such as antigen-antibody reactions, physical trapping of particles,receptor site binding, removal of intentionally damaged cells fromcirculation, and transport of a chemical species across a cell membraneand into the cell by a normally operative metabolic process. A summaryof the mechanisms of localization by radiopharmaceuticals is describedin http://www.lunis.luc.edu/nucmed/tutorial/radpharm/i.htm. For example:

1. Active transport involves the use of a normally operative metabolicpathway in the body, for moving a radiopharmaceutical across a cellmembrane and into the cell. An example of a radiopharmaceutical that maybe used for active transport is I¹³¹ in the form of NaI, for thyroidimaging.

2. Phagocytosis involves physical entrapment of colloidal particles byKupffer cells in the RE System. An example of a radiopharmaceutical thatmay be used for phagocytosis is Tc^(99m) in the form of sulfur colloid,for liver and spleen imaging.

3. Capillary blockage involves intentional microembolization of acapillary bed with particles. An example of a radiopharmaceutical thatmay be used for capillary blockage is Tc^(99m) in the form of MAA, forpulmonary perfusion imaging.

4. Cell sequestration involves injection of damaged RBC's to produce aspleen scan with no visualization of the liver. An example of aradiopharmaceutical that may be used for cell sequestration is heatdamaged autologous Tc^(99m) RBC's.

5. Simple or exchange diffusion involves a mechanism whereby aradiotracer diffuses across cell membranes and then binds or attachesitself to a cell component. An example of a radiopharmaceutical that maybe used for simple or exchange diffusion is F¹⁸, in the form of NaF, forbone imaging.

6. Compartmental Localization involves placement of a radiotracer in afluid space and imaging of that fluid space. Examples ofradiopharmaceuticals that may be used for compartmental localization areTc^(99m) HAS, for MUGA's, In¹¹¹ DTPA, for cistemograms, and Xe¹³³ gasfor pulmonary perfusion.

7. Chemisorption involves surface binding of radiopharmaceutical to asolid structure. An example of a radiopharmaceutical that may be usedfor chemisorption is In¹¹¹ platelets bound to a surface of an activethrombus.

8. Antigen or antibody reaction involves uptake at tumor site due tospecific binding of radiolabeled antibody to surface antigens on tumors.Examples of radiopharmaceuticals that may be used for antigen orantibody reaction are In¹¹¹ Oncoscint, for the localization of recurrentovarian or colorectal carcinoma, or In¹¹¹ ProstaScint for thelocalization or recurrent cancer.

9. Receptor binding involves the binding of a radiopharmaceutical tohigh-affinity receptor sites. An example of a radiopharmaceutical thatmay be used for receptor binding is In¹¹¹ octreotide, for localizationof neuroendocrine and other tumors based on binding of a somatostatinanalog to receptor sites in tumors.

Examples of other radiopharmaceuticals include the following:

1. anti-CEA, a monoclonal antibody fragment, which targets CEA—producedand shed by colorectal carcinoma cells—and may be labeled by Tc^(99m) orby other radioisotopes, for example, iodine isotopes (Jessup J M, 1998,Tumor markers—prognostic and therapeutic implications for colorectalcarcinoma, Surgical Oncology; 7: 139-151);

2. In¹¹¹-Satumomab Pendetide (Oncoscint®), designed to target TAG-72, amucin-like glycoprotein, expressed in human colorectal, gastric,ovarian, breast and lung cancers, but rarely in healthy human adulttissues (Molinolo A; Simpson J F; et al., 1990, Enhanced tumor bindingusing immunohistochemical analyses by second generationanti-tumor-associated glycoprotein 72 monoclonal antibodies versusmonoclonal antibody B72.3 in human tissue, Cancer Res., 50(4): 1291-8);

3. Lipid-Associated Sialic Acid (LASA), a tumor antigen, used forcolorectal carcinoma, with a similar sensitivity as anti-CEA monoclonalantibody fragment but a greater specificity for differentiating betweenbenign and malignant lesions (Ebril K M, Jones J D, Klee G G, 1985, Useand limitations of serum total and lipid-bound sialic acidconcentrations as markers for colorectal cancer, Cancer; 55:404-409);

4. Matrix Metaloproteinase-7 (MMP-7), a proteins enzyme, believed to beinvolved in tumor invasion and metastasis (Mori M, Barnard G F et al.,1995, Overexpression of matrix metalloproteinase-7 mRNA in human coloncarcinoma, Cancer; 75: 1516-1519);

5. Ga⁶⁷ citrate, used for detection of chronic inflammation (Mettler FA, and Guiberteau M J, Eds., 1998, Inflammation and infection imaging,Essentials of nuclear medicine, Fourth edition, Pgs: 387-403);

6. Nonspecific-polyclonal immunoglobulin G (IgG), which may be labeledwith both In¹¹¹ or Tc^(99m), and which has a potential to localizenonbacterial infections (Mettler F A, and Guiberteau M J, ibid);

7. Radio-labeled leukocytes, such as such as In¹¹¹ oxine leukocytes andTc^(99m) HMPAO leukocytes, which are attracted to sites of inflammation,where they are activated by local chemotactic factors and pass throughthe endothelium into the soft tissue (Mettler F A, and Guiberteau M J,ibid; Corstens F H; van der Meer J W, 1999, Nuclear medicine's role ininfection and inflammation, Lancet; 354 (9180): 765-70); and

8. Tc^(99m) bound to Sodium Pertechnetate, which is picked up by redblood cells, and may be used for identifying blood vessels and vitalorgans, such as the liver and the kidneys, in order to guide a surgicalinstrument without their penetration.

The particular choice of a radionuclide for labeling antibodies dependsupon the chemistry of the labeling procedure and the isotope nuclearproperties, such as, the number of gamma rays emitted, their respectiveenergies, the emission of other particles, such as beta or positrons,the isotope half-life, and the existence of different isotopes ofidentical chemistry but different half-lives (e.g., I¹³¹ and I¹³³). Theusual preferred emission for medical applications is that of gamma rays,with an energy range of approximately 11-511 KeV. However, beta andpositron radiation may also be detected.

The detector may be a room temperature, solid-state CdZnTe (CZT)detector, configured as a single-pixel or a multi-pixel detector,obtained, for example, from eV Products, a division of II-VICorporation, Saxonburg Pa., 16056, or from IMARAD IMAGING SYSTEMS LTD.,of Rehovot, ISRAEL, 76124, www.imarad.com, or from another source.Alternatively, another solid-state detector such as CdTe, HgI, Si, Ge,or the like, or a scintillation detector (such as NaI(Tl), LSO, GSO,CsI, CaF, or the like, or a combination of a scintillation detector anda photomultiplier, to form an Anger camera, or another detector asknown, may be used.

FIGS. 1A and 1B schematically illustrate a detecting unit 12 and a block90 of detecting units 12, respectively, as known.

As seen in FIG. 1A, the detecting unit 12 is formed of a single-pixeldetector 91, having a diameter D and a thickness τ_(d). Both thedetector diameter D, or a diameter equivalent, in the case of anon-circular detector, and the detector thickness τ_(d) affect thedetecting efficiency. The detector diameter D determines the surfacearea on which radioactive emission impinges; the greater the surfacearea, the greater the efficiency. The detector thickness τ_(d) affectsthe stopping power of the detector. High energy gamma rays may gothrough a thin detector; the probability of their detection increaseswith the detector thickness τ_(d).

FIG. 1A illustrates a single-pixel detector 91, which by itself cannotgenerate an image; rather, all counts are distributed over the surfacearea of the detector 91.

As seen in FIG. 1B, the block 90 includes a plurality of the detectingunit 12, formed by dividing the detector 91 into a plurality ofelectrically insulated pixels 106, each associated with a collimator 96.The collimators 96 are of the diameter or diameter equivalent D, alength L, and a septa thickness τ. The collimators 96 may be, forexample, of lead, tungsten or another material which substantiallyblocks gamma and beta rays. The collimators 96 may be shaped as tubes,rectangular grids, or grids of another polygon. Wide-angle ornarrow-angle collimators are also possible.

The collimator's geometry, and specifically, the ratio of D/L, providesthe detecting unit 12 with a collection solid angle δ analogous to aviewing solid angle of an optical camera. The collection solid angle δlimits the radioactive-emission detection to substantially only thatradioactive emission, which impinges on the detector 91 after passingthrough a “corridor” of the collimator 96 (although in practice, somehigh-energy gamma rays may penetrate the collimator's walls). With nocollimator, the collection angle δ, is essentially a solid angle of 4πsteradians.

Thus, the collimator's geometry affects both the detection efficiencyand the image resolution, which are defined as follows:

-   i. The detection efficiency is the ratio of measured radiation to    emitted radiation; and-   ii. The image resolution is the capability of making distinguishable    closely adjacent manifestations of a pathology, or the capability to    accurately determine the size and shape of individual manifestations    of a pathology.

Naturally, it is desired to optimize both the detection efficiency andthe image resolution. Yet, they are inversely related to each other. Thedetection efficiency increases with increasing collimator's collectionangle, and the image resolution decreases with increasing collimator'scollection angle.

In other words, while a wide-aperture, single-pixel detecting unit, suchas that of FIG. 1A provides high efficiency, it does not lend itself tothe generation of a two-dimensional image, and the wide aperture blursthe information regarding the direction from which the radiation comes.Yet as the resolution is increased, for example, to the detecting unit12 of FIG. 1B, the detection efficiency is decreased.

Commonly owned US Applications 20040015075 and 20040054248 and commonlyowned PCT publication WO2004/042546, all of whose disclosures areincorporated herein by reference, describe systems and methods forscanning a radioactive-emission source with aradioactive-emission-measuring probe of a wide-aperture collimator, andat the same time, monitoring the position of theradioactive-emission-measuring probe, at very fine time intervals, toobtain the equivalence of fine-aperture collimation. In consequence,high-efficiency, high-resolution images of a radioactivity emittingsource are obtained.

A system according to US Applications 20040015075 and 20040054248 andPCT publication WO2004/042546 is seen in FIGS. 2-3B.

FIG. 2 schematically illustrates the basic component of a system 120,comprising a radioactive-emission-measuring probe 122 and aposition-tracking device 124, both in communication with a dataprocessing unit 126. The radioactive-emission-measuring probe 122 isassociated with a first coordinate system 128, and the position-trackingdevice 124 is associated with a second coordinate system 128′, whereinthe position-tracking device 124 monitors the position of theradioactive-emission-measuring probe 122 as a function of time. The dataprocessing unit 126 processes the measurements of both theradioactive-emission-measuring probe 122 and the position-trackingdevice 124 and combines them, to form the image.

FIG. 3A schematically illustrates the manner of operating theradioactive-emission-measuring probe 122 with the position-trackingdevice 124 of the system 120. The radioactive-emission-measuring probe122 moves about an area of radioactive emission 110, for example, in thedirection of an arrow 118, so as to measure a radioactive emissiondistribution 112, as a function of time, while the position-trackingdevice 124 monitors the position of probe 122. Theradioactive-emission-measuring probe 122 may be a single-pixel detectorof high efficiency, which is incapable, by itself, of producing images.Nonetheless, a data processing unit 126, processes aradioactive-count-rate input 121 together with a position-tracking input123, using algorithms 125, to reconstruct an image 110′ of the area ofradioactive emission 110, for example, on a display unit 129.

Images according to this concept are illustrated in FIGS. 3B-3B. Thearea of radioactive emission 110 is located in a two-dimensionalcoordinates u;v, and includes two hot points 115 (FIG. 3B). The system120 moves from a position P(1) at a time t(1), to a position P(2) at atime t(2), while measuring the radioactive emission distribution 112 ofthe area of radioactive emission 110, including the hot points 115.

An example of a suitable position-tracking device 124 is miniBird™,which is a magnetic tracking and location system commercially availablefrom Ascension Technology Corporation, P.O. Box 527, Burlington, Vt.05402 USA (http://www.ascension-tech.com/graphic.htm). The miniBird™measures the real-time position and orientation (in six degrees offreedom) of one or more miniaturized sensors, so as to accurately trackthe spatial location of probes, instruments, and other devices. Thedimensions of miniBird™ 124 are 18 mm×8 mm×8 mm for the Model 800 and 10mm×5 mm×5 mm the Model 500. Alternatively, an optical tracking device,of Northern Digital Inc., Ontario, Canada NDI-POLARIS, which providespassive or active systems, a magnetic tracking device of NDI-AURORA, aninfrared tracking device of E-PEN system, http://www.e-pen.com, or anultrasonic tracking device of E-PEN system may be used. Additionally oralternatively, the position-tracking device may be an articulated-armposition-tracking device, an accelerometer-based position-trackingdevice, a potentiometer-based position-tracking device, or aradio-frequency-based position-tracking device.

Commonly owned US application 20040054248 and commonly owned PCT topublication WO2004/042546 further disclose various extracorporeal andintracorporeal systems 120, of radioactive-emission-measuring probes122, of relatively wide apertures, associated with position-trackingdevices 124. Examples of extracorporeal and intracorporealradioactive-emission-measuring probes of this type, operative withposition-tracking devices, are seen in FIGS. 4A-4C.

FIG. 4A schematically illustrates a hand-held, extracorporeal probe 170,formed as the system 120, and having the radioactive-emission-measuringprobe 122 of a detector 132, a collimator 134 and a controller 130, andfurther including the position-tracking device 124, wherein theradioactive-emission-measuring probe 122 and the position-trackingdevice 124 are associated with the data processing unit 126, as taughtin conjunction with FIGS. 2-3B.

FIG. 4B schematically illustrates an intracorporeal probe 180, formed asthe system 120, mounted on a catheter 136, and having theradioactive-emission-measuring probe 122, of the detector 132 and thecollimator 134, and the position-tracking device 124, wherein the probe122 and the position tracking device 124 are associated with the dataprocessing unit 126, as taught in conjunction with FIGS. 2-3B. Theintracorporeal probe 180 is configured to penetrate a tissue 135, via atrucar valve 138. A structural imager, such as an ultrasound imager 137or an MRI probe 137 may further be included.

FIG. 4C schematically illustrates an intracorporeal probe 190, formed asthe system 120, adapted for rectal insertion and having theradioactive-emission-measuring probe 122, formed as a plurality ofdetectors 132 and collimators 134, and associated with theposition-tracking device 124. The intracorporeal probe 190 may befurther adapted for motion along the x and ω directions. For example,the intracorporeal probe 190 may include a motor 154 for self-motion inthe x and ω directions, so as to crawl into the rectum. The motor 154may be obtained, for example, from B-K Medical A/S, of Gentofte, DK, andmay be adapted to report to the data processing unit 126 the exactposition and orientation of the intracorporeal probe 190, based on thenumber of rotations. In some embodiments, the motor 154 is used in placeof the position-tracking device 124. Alternatively, it is used inaddition to it. The intracorporeal probe 190 may further include thestructural imager 137, such as an ultrasound imager or an MRI probe.

The acquisition of both a functional image of the body, such as aradioactive-emission image, and a structural image, such as anultrasound, an x-ray, or an MRI image, and their co-registration on asingle frame of reference, is disclosed by commonly owned U.S. Pat. No.6,173,201 to Front, whose disclosure is incorporated herein byreference, as well as by M. W. Vannier and D. E. Gayou, “Automatedregistration of multimodality images”, Radiology, vol. 169 pp. 860-861(1988); J. A. Correia, “Registration of nuclear medicine images, J.Nucl. Med., vol. 31 pp. 1227-1229 (1990); J-C Liehn, A. Loboguerrero, C.Perault and L. Demange, “superposition of computed tomography and singlephoton emission tomography immunoscinigraphic images in the pelvis:validation in patients with colorectal or ovarian carcinoma recurrence”,Eur. J. Nucl. Med., vol. 19 pp. 186-194 (1992); F. Thomas et al.,“Description of a prototype emission transmission computed tomographyimaging system”, J. Nucl. Med., vol. 33 pp. 1881-1887 (1992); D. A.Weber and M. Ivanovic, “Correlative image registration”, Sem. Nucl.Med., vol. 24 pp. 311-323 (1994); and Hasegawa et al., U.S. Pat. No.5,376,795.

In essence, several images may be acquired and co-registered to the sameframe of reference, as follows:

-   i. a first functional image scan, based for example, on anti-CEA    monoclonal antibody fragment, labeled by iodine isotopes, may be    acquired for targeting CEA—produced and shed by colorectal carcinoma    cells for detecting a pathological feature, such as colorectal    carcinoma;-   ii. a second functional image, based for example, on    nonspecific-polyclonal immunoglobulin G (IgG), which may be labeled    with Tc^(99m), may be acquired for locating blood vessels and vital    structures, such as the heart, or the stomach, co-registered with    the first functional image and the pathological feature detected on    it, in order to locate the pathological feature in reference to    blood vessels and vital organs; and-   iii. a structural image, such as an ultrasound image, may be used    for general structural anatomy, co-registered with the first and    second functional images, in order to locate the pathological    feature in reference to bones and the general anatomic structure.

In this manner, a physician may locate the pathological feature inreference to the blood vessels, vital organs, and the bones.

Additionally, correlation may be used to guide a minimally invasivesurgical instrument to the pathological feature, while avoiding theblood vessels, vital organs, and bones. The minimally invasive surgicalinstrument may be a biopsy needle, a wire, for hot resection, a knifefor cold resection, an instrument of focused energy, to produceablation, for example, by ultrasound, or by laser, an instrument forcryosurgery, an instrument for croyetherapy, or an instrument forbractherapy, wherein seeds of a radioactive metal are planted close to atumor, for operating as a radioactive source near the tumor.

Commonly owned PCT publication WO2004/042546 further discloses that thesurgical instrument may be visible on at least one of the images, forexample, on the structural image, to enable the physician to see theinstrument, the pathological feature, and the surrounding anatomy on thedisplay 129 (FIG. 3A). Additionally, the surgical instrument may beradioactively labeled, to be visible also on the functional image.

Commonly owned U.S. Pat. No. 6,173,201 discloses a method ofstereotactic therapy, wherein a frame, which includes at least threemarkers, visible on a structural image, is rigidly secured to a patient.The structural image of a region inside the patient's body, whichincludes a pathological feature and the markers, is acquired. Afunctional image of the pathological feature is then acquired andco-registered with the structural image, to correlate the images to thesame frame of reference. A stereotactic guide is rigidly attached to theframe and is used to guide a surgical instrument, such as a biopsyneedle or a brachytherapy needle, to the pathological feature, withreference to the co-registered images.

Commonly owned PCT publication WO2004/042546 further disclosures the useof a structural image, such as of ultrasound or MRI, for informationabout tissue attenuation. The information may then be used to correctthe radioactive-emission measurements.

Nuclear imaging for coronary artery disease is also known. For example,U.S. Pat. No. 6,597,940, to Bishop, et al, relates to screening patientsfor an early stage of coronary artery disease. According to this method,a patient is screened based on the time-activity curve for a radioactivetracer passing through a left ventricle region of the patient's body.According to another aspect of the invention, an array of gamma particledetectors is employed to obtain data for a region of interest that islarger than and encompasses a left ventricle region of the patient'sbody. An analysis of the data identifies the subset of the region ofinterest that corresponds to the left ventricle region. According to afurther aspect of the present invention, a second technique is employedto locate the left ventricle region. A still further aspect of thepresent invention relates to obtaining images of a patient's heart usinga high temporal resolution gamma camera.

Additionally, U.S. Pat. No. 6,671,541, to Bishop et al. relates to acardiovascular imaging and functional analysis system and method,wherein a dedicated fast, sensitive, compact and economical imaginggamma camera system that is especially suited for heart imaging andfunctional analysis is employed. The cardiovascular imaging andfunctional analysis system of the present invention can be used as adedicated nuclear cardiology small field of view imaging camera. Thedisclosed cardiovascular imaging system and method has the advantages ofbeing able to image physiology, while offering an inexpensive andportable hardware, unlike MRI, CT, and echocardiography systems. Thecardiovascular imaging system of the invention employs a basic modulardesign suitable for cardiac imaging with one of several radionucleidetracers. The detector can be positioned in close proximity to the chestand heart from several different projections, making it possible rapidlyto accumulate data for first-pass analysis, positron imaging,quantitative stress perfusion, and multi-gated equilibrium pooled blood(MUGA) tests. In a preferred embodiment, the Cardiovascular Non-InvasiveScreening Probe system can perform a novel diagnostic screening test forpotential victims of coronary artery disease. The system provides arapid, inexpensive preliminary indication of coronary occlusive diseaseby measuring the activity of emitted particles from an injected bolus ofradioactive tracer. Ratios of this activity with the time progression ofthe injected bolus of radioactive tracer are used to perform diagnosisof the coronary patency (artery disease).

SUMMARY OF THE INVENTION

The present invention successfully addresses the shortcomings of thepresently known configurations by providing systems, methods, and probesfor functional imaging by radioactive-emission-measurements, specific tobody structures, such as the prostate, the esophagus, the cervix, theuterus, the ovaries, the heart, the breast, the brain, and the wholebody, and other body structures. The nuclear imaging may be performedalone, or together with structural imaging, for example, by x-rays,ultrasound, or MRI. Preferably, the radioactive-emission-measuringprobes include detectors, which are adapted for individual motions withrespect to the probe housings, to generate views from differentorientations and to change their view orientations. These motions areoptimized with respect to functional information gained about the bodystructure, by identifying preferred sets of views for measurements,based on models of the body structures and information theoreticmeasures. A second iteration, for identifying preferred sets of viewsfor measurements of a portion of a body structure, based on models of alocation of a pathology that has been identified, makes it possible, ineffect, to zoom in on a suspected pathology. The systems arepreprogrammed to provide these motions automatically.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. In case of conflict, the patentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and not intendedto be limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIGS. 1A-1B schematically illustrate detecting units and blocks forradioactive emission detection as known;

FIG. 2 schematically illustrates the basic component of a system,comprising a radioactive-emission-measuring probe and aposition-tracking device, both in communication with a data processingunit;

FIGS. 3A-3B schematically illustrate the manner of operating theradioactive-emission-measuring probe with the position-tracking device;

FIGS. 4A-4C schematically illustrate extracorporeal and intracorporealradioactive-emission-measuring probes operative with position-trackingdevices;

FIGS. 5A-5F present the principles of modeling, for obtaining an optimalset of views, in accordance with embodiments of the present invention;

FIGS. 6A and 6B pictorially illustrate a view and viewing parametersassociated with it, in accordance with definitions of the presentinvention;

FIGS. 7A-7C schematically illustrate anatomical constraints, which areto be modeled, in accordance with embodiments of the present invention;

FIG. 8 illustrates, in flowchart form, a method of predefining a set ofviews for functional imaging, tailored for imaging from esophagus, andoptimized with respect to the functional information gained about thebody structure, in accordance with embodiments of the present invention;

FIGS. 9A-9F schematically illustrate possible models and collections ofviews, for a body structure, in accordance with embodiments of thepresent invention;

FIG. 10 illustrates, in flowchart form, a method of functional imaging,tailored for imaging from esophagus, and optimized with respect to thefunctional information gained about the body structure, in accordancewith embodiments of the present invention;

FIG. 11 schematically illustrates the process of modeling in twoiterations, for zooming in on a pathological feature, in accordance withembodiments of the present invention;

FIG. 12 illustrates, in flowchart form, a method of several iterationsfor zooming in on a pathological feature, when performing in vivomeasurements, in accordance with embodiments of the present invention;

FIGS. 13A-13E schematically illustrate possible probe designs, and theprocess of obtaining views based on a model and a probe design, inaccordance with embodiments of the present invention;

FIG. 14 illustrates, in flowchart form, a method of selecting a probedesign optimized with respect to information gained about a bodystructure, in accordance with embodiments of the present invention;

FIG. 15 illustrates, in flowchart form, a method of selecting a probedesign, based on the rate of data collection and other designconsiderations, in accordance with embodiments of the present invention;

FIGS. 16A-16L schematically illustrate the process of obtaining viewswith the radioactive-emission-measuring probe, based on a modeledvolume, in accordance with embodiments of the present invention;

FIGS. 16M-16U schematically illustrate experimental results, obtainedwith the radioactive-emission-measuring probe, for a modeled volumehaving organ targets, in accordance with embodiments of the presentinvention;

FIGS. 17A-17L schematically illustrate various detecting units andblocks, which may be incorporated in probe designs;

FIGS. 18A-18D schematically illustrate possible motions of aradioactive-emission-measuring probe, for a single detecting unit and asingle block, in accordance with embodiments of the present invention;

FIGS. 19A-19E schematically illustrate other possible motions of aradioactive-emission-measuring probe, for a single block, in accordancewith embodiments of the present invention;

FIGS. 20A-20H schematically illustrate possible motions of aradioactive-emission-measuring probe, having a plurality of pairs ofradioactive-emission blocks;

FIGS. 21A-21D schematically illustrate other possible motions of aradioactive-emission-measuring probe, having a plurality of pairs ofradioactive-emission blocks;

FIGS. 22A-22H schematically illustrate a radioactive-emission-measuringprobe system, comprising a plurality of assemblies, each formed as theprobe system of FIGS. 20A-20H, in accordance with embodiments of thepresent invention;

FIGS. 23A-23D schematically illustrate aradioactive-emission-measuring-probe system, in accordance withembodiments of the present invention;

FIGS. 24A-24C schematically illustrate the modeling of a prostate as ato process of two iterations, for zooming in on a pathology, inaccordance with embodiments of the present invention;

FIGS. 25A-25E schematically illustrate the external appearance and theinternal structure of the radioactive-emission-measuring probe for theprostate, in accordance with an embodiment of the present invention;

FIG. 26 illustrates further the internal structure of theradioactive-emission-measuring probe for the prostate, in accordancewith an embodiment of the present invention;

FIG. 27 schematically illustrates the radioactive-emission-measuringprobe for the prostate, integrated with an ultrasound probe, inaccordance with another embodiment of the present invention;

FIG. 28 schematically illustrates an ultrasound wave impinging on aprostate, in accordance with embodiments of the present invention;

FIGS. 29A-29C illustrate the fusing of a radioactive-emission image andan ultrasound image, in accordance with embodiments of the presentinvention;

FIG. 30 schematically illustrates the radioactive-emission-measuringprobe for the prostate, integrated with a surgical needle, in accordancewith another embodiment of the present invention;

FIGS. 31 and 32 schematically illustrate the operation of the surgicalneedle of FIG. 30;

FIG. 33 schematically illustrates the modeling of the femalereproductive system as a process of two iterations, for zooming in on apathology, in accordance with embodiments of the present invention;

FIGS. 34A-34R schematically illustrate radioactive-emission measuringprobes 600, tailored for imaging the woman's reproductive system andoptimized with respect to the functional information gained, regardingthe body structures of the woman's reproductive system, in accordancewith embodiments of the present invention;

FIGS. 35A-35Q schematically illustrate radioactive-emission measuringprobes 600, adapted for the esophagus, in accordance with embodiments ofthe present invention;

FIG. 35R schematically illustrates an esophagus nearby organs;

FIG. 35S schematically illustrates a stomach and nearby organs;

FIGS. 36A-36C schematically illustrate a heart;

FIGS. 37A-37D schematically illustrate the basic components of thecardiac probe system, in accordance with embodiments of the presentinvention;

FIG. 38 schematically illustrates the chair and the probe assembly,arranged for operation, in accordance with an embodiment of the presentinvention;

FIGS. 39A-39B schematically illustrate possible inner structures of theprobe assembly, in accordance with preferred embodiments of the presentinvention;

FIGS. 40A and 40B schematically illustrate an assembly and a block, inaccordance with an embodiment of the present invention

FIG. 41 further illustrates a block, in accordance with a preferredembodiment of the present invention;

FIG. 42 schematically illustrates the cardiac model, in accordance witha preferred embodiment of the present invention;

FIGS. 43A-43E schematically illustrate blocks, arranged for viewing thecardiac model, in accordance with a preferred embodiment of the presentinvention;

FIG. 44 schematically illustrates a dual imaging system forradioactive-emission-measurements in tandem with a three-dimensionalstructural imager, in accordance with a preferred embodiment of thepresent invention;

FIG. 45 schematically illustrates a cross-sectional view of dual imagingsystem for radioactive-emission-measurements in tandem with athree-dimensional structural imager, in accordance with a preferredembodiment of the present invention;

FIGS. 46A-46C schematically illustrate possible inner structures andarrangement of the probe of the dual imaging system, in accordance withpreferred embodiments of the present invention;

FIGS. 47A and 47B schematically illustrate the assembly 92 and the block90, in accordance with a preferred embodiment of the present invention;

FIGS. 48A-48B present the principles of modeling, for obtaining anoptimal set of views, for a brain, in accordance with embodiments of thepresent invention;

FIG. 49 pictorially illustrates a method for zooming in on a suspectedto pathological feature in a brain, as a process of two or moreiterations, in accordance with embodiments of the present invention;

FIGS. 50A-50C schematically illustrate theradioactive-emission-measuring probe for the brain, in accordance withembodiments of the present invention;

FIGS. 51A-51K schematically illustrate inner structures of the probe forthe brain, in accordance with several embodiments of the presentinvention;

FIG. 52A pictorially illustrates a method for zooming in on a suspectedpathological feature in a breast, as a process of two or moreiterations, in accordance with an embodiment of the present invention;FIG. 52B pictorially illustrates a method for zooming in on a suspectedpathological feature in a breast, when held between support andcompression plates, as a process of two or more iterations, inaccordance with another embodiment of the present invention;

FIG. 53A schematically illustrates a basic mammograph;

FIGS. 53B and 53C schematically illustrate a mammograph configured forultrasound imaging, and a mammograph configured for ultrasound imagingwith a surgical instrument, respectively, in accordance with embodimentsof the present invention;

FIGS. 54A-54E schematically illustrate an assembly, configured foroperation with a mammoraph-like radioactive-emission-measuring probe forthe breast, in accordance with embodiments of the present invention;

FIGS. 55A-55K schematically illustrate radioactive-emission-measuringprobes for the breast, wherein the breast is compressed between twoplates, in accordance with embodiments of the present invention;

FIGS. 56A-56C schematically illustrate a radioactive-emission-measuringprobe 930, for imaging a breast under vacuum, in accordance with anotherpreferred embodiment of the present invention; and

FIGS. 57A-57F schematically illustrate a radioactive-emission-measuringprobe 950, for imaging the breasts in the natural state, in accordancewith another preferred embodiment of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to of systems, methods, and probes forfunctional imaging by radioactive-emission-measurements, specific tobody structures, such as the prostate, the esophagus, the cervix, theuterus, the ovaries, the heart, the breast, the brain, and the wholebody, and other body structures. The nuclear imaging may be performedalone, or together with structural imaging, for example, by x-rays,ultrasound, or MRI. Preferably, the radioactive-emission-measuringprobes include detectors, which are adapted for individual motions withrespect to the probe housings, to generate views from differentorientations and to change their view orientations. These motions areoptimized with respect to functional information gained about the bodystructure, by identifying preferred sets of views for measurements,based on models of the body structures and information theoreticmeasures. A second iteration, for identifying preferred sets of viewsfor measurements of a portion of a body structure, based on models of alocation of a pathology that has been identified, makes it possible, ineffect, to zoom in on a suspected pathology. The systems arepreprogrammed to provide these motions automatically.

The principles and operation of the radioactive-emission-measuringsystems, probes and methods, according to embodiments of the presentinvention, may be better understood with reference to the drawings andaccompanying descriptions.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Referring now to the drawings, FIGS. 5A-5F present the principles ofmodeling, for obtaining an optimal set of views, in accordance withembodiments of the present invention.

FIG. 5A schematically illustrates a body section 230, having a region ofinterest (ROI) 200. The region of interest 200 may be associated with abody structure 215, with a specific radioactive-emission-densitydistribution, possibly suggestive of a pathological feature 213, termedherein an organ target 213. Additionally, there may be certain physicalviewing constraints, associated with the region of interest 200.

We thus consider the following problem: how can we best identify anoptimal and permissible set of views for radioactive-emissionmeasurements of the region of interest 200, for reconstructing athree-dimensional image of it?

In accordance with embodiments of the present invention, our approach isdelineated in FIG. 5C, by a method 205, as follows:

-   in a box 206: modeling the region of interest 200, as a model 250 of    a volume U, possibly with one or several modeled organ targets HS,    within anatomical constraints AC, as seen in FIG. 5B;-   in a box 207: obtaining an optimal and permissible set of views for    the modeled volume U FIG. 5B; and-   in a box 208: applying the optimal set of views to the in-vivo    region of interest 200 and the body structure 215 of FIG. 5A.

It will be appreciated that the model 250 of the region of interest 200may be based on general medical information of the body structure 215and common pathological features associated with it. Additionally, themodel may be based on information related to a specific patient, such asage, sex, weight, and body type. Furthermore, a structural image, suchas by ultrasound or MRI, may be used for providing information about thesize and location of the body structure 215 in relation to the bodysection 230, for generating the model 250.

FIGS. 5D-5F schematically illustrate three types of the modeled organtargets HS, as follows:

-   i. a region of concentrated radiation, or a hot region, for example,    as may be associated with a malignant tumor and as seen in FIG. 5D;-   ii. a region of low-level radiation, which is nonetheless above    background level, for example, as may be associated with carcinoma    and as seen in FIG. 5E, and-   iii. a region of little radiation, or a cold region, below the    background level, for example, as may be associated with dead tissue    and as seen in FIG. 5F.

Referring further to the drawings, FIGS. 6A and 6B pictoriallyillustrate a view and viewing parameters associated with it, inaccordance with definitions of the present invention.

Seen in FIG. 6A is the volume U, subdivided into voxels u. The volume Uto is defined in a six-degree coordinate system x;y;z;ω;θ;σ and has apoint of origin P0(x0; y0; z0; ω0; θ0; σ0). A detecting unit 12 ispositioned at a location and orientation P1(x1; y1; z1; ω1; θ1; σ1). Thedetecting unit 12 has a detector 91 of a specific detector material of athickness t, and a collimator 96 of a diameter D and a length L, so asto define a collection angle δ.

FIG. 6B schematically illustrates the emission rate of the volume U, asa function of time, given that a radioactive material of a specifichalf-life has been administered at a time T0.

A view may thus be defined as a group of nonzero probabilities ofdetecting a radioactive emission associated with all the voxels thatform a sector S (FIG. 6A). A view is sometimes referred to as aprojection, and the two terms are synonymous. Furthermore, a viewdefined over a sector S can be naturally extended to be defined over theset of all voxels, by simply associating a zero probability with everyvoxel outside the S. This makes possible the application of mathematicaloperations over the entire volume U.

A view is dependent on the following viewing parameters:

Location and Orientation Parameters:

A location and an orientation in a six-dimensional space, P1(x1; y1; z1;ω1; θ1; σ1), with respect to the origin P0(x0; y0; z0; ω0; θ0; σ0) ofthe volume U, in which the detecting unit 12 is positioned;

Detecting-Unit Parameters:

-   -   The collection angle δ, which together with the location and        orientation parameters, P1(x1; y1; z1; ω1; θ1; σ1) with respect        to the origin P0(x0; y0; z0; ω0; θ0; σ0) define the sector S;    -   The detector material, which affects the detector efficiency;    -   The detector thickness t, which affects the detector's stopping        power, hence, its efficiency; and    -   The diameter of the detecting unit, or the effective diameter,        calculated so as to produce a circle of the same area, when the        geometry is not a circle;        Attenuation Parameters:

Attenuation properties of all the voxels within the sector S, as theyaffect the probabilities that radioactive emissions from a specificvoxel within the sector S will reach the detector, wherein differentvoxels within the sector S may have different attenuation properties,since several types of tissue may be involved;

Radiopharmaceutical Parameters:

The half life t_(1/2), of the radiopharmaceutical, the types ofradioactive emission, whether gamma or beta, and the energies of theradioactive emission affect the probability of detection; and

Time Parameters:

Given that T0 is the time of administrating the radiopharmaceutical, thetime T1 since administration, and the duration of the measurement ΔT1,affect the number of emissions that occur during theradioactive-emission measurement.

Some of these viewing parameters are fixed for a particular situation.Specifically, the tissue attenuation parameters are given. Additionally,the time T1 since administration of the radiopharmaceutical is generallygoverned by the blood pool radioactivity, since it is generallynecessary to wait until the blood pool radioactivity dies out forlow-level detection to be possible. For the remaining viewingparameters, optimization may be carried out.

The remaining viewing parameters may be divided into two categories:

-   i. viewing parameters in the design of a    radioactive-emission-measuring probe;-   ii. viewing parameters for an optimal set of views, for a given    probe.    Viewing Parameters for an Optimal Set of Views, for a Given Probe

Referring further to the drawings, FIGS. 7A-7C schematically illustrateanatomical constraints, which may hinder measurements.

FIG. 7A schematically illustrates the region of interest 200, for whicha three-dimensional radioactive-emission image is desired. The region ofinterest 200 is in free space, with no constraints to limitaccessibility to it. Thus, a radioactive-emission-measuring probe 210may travel, for example, along tracks 202 and 204, and any other track,unhindered.

In FIG. 7B, the region of interest 200 is associated with the bodystructure 215, such as a prostrate, in vivo. For obtaining aradioactive-emission image, the radioactive-emission-measuring probe 210may be inserted transrectally, so as to travel in a rectum 206, forexample, in the direction of an arrow 208. Its ability to image theprostrate is limited by anatomical constraints.

In FIG. 7C, the region of interest 200 is associated with the bodystructure 215, such as a body structure, in vivo, and theradioactive-emission-measuring probe 210 may be an extracorporeal probe,which may perform radioactive-emission measurements from outside thebody, on an extracorporeal surface 214, for example when moving along atrack 212.

In each of these cases, it is desired that a reconstructedthree-dimensional radioactive-emission image of the region of interest200 be obtained, at a predetermined quality. This is achieved bypredefining an optimal set of radioactive-emission measurement views,tailored to the specific organ 215 and optimized with respect to theinformation gained, regarding the body structure 215.

Referring further to the drawings, FIG. 8 illustrates, in flowchartform, a method 300 for predefining a set of radioactive-emissionmeasurement views, for functional imaging, tailored for imaging fromesophagus and optimized with respect to the functional informationgained, regarding the body structure 215, in accordance with embodimentsof the present invention. The method 300 comprises:

-   in a box 302: providing a model of the body structure 215, based on    its geometry;-   in a box 304: providing a model of anatomical constraints, which    limit accessibility to the body structure;-   in a box 306: providing a collection of views of the modeled body    structure, obtained within the modeled anatomical constraints;-   in a box 308: providing a scoring function, by which any set of at    least one view, from a collection of views is scorable with a score    that rates information, obtained from the modeled body structure by    the set;-   in a box 310: forming sets of views from the collection of views and    scoring them, with the scoring function; and-   in a box 312: selecting a set of views, from the collection of    views, based on its score, as the predefined set of views.

The model of the body structure is based on anatomical knowledgeregarding its size, shape, and weight. In fact different models may beprovided, for example, for to different ages, sexes, weights, and bodytypes, such as heavy-built, medium-built, or small-built. In accordancewith a first embodiment, the body structure is modeled assuming noradioactive emission throughout its volume. In accordance with otherembodiments, the body structure may be modeled with one or more modeledorgan targets, simulating different pathological features. Specifically,the modeled organ targets may be hot regions, of a radioactive-emissionintensity, higher than the background level, regions of low-levelradioactive-emission intensity, which is nonetheless above thebackground level, and cold regions, of a radioactive-emission intensity,lower than the background level. These may be distributed in accordancewith medical records, which teach of sites within the body structurethat may be more susceptible to certain pathologies.

Similarly, the model of anatomical constraints, which limitaccessibility to the body structure, is based on anatomical knowledge,and different models may be provided, for example, for different ages,sexes, weights, and body types.

The collection of views may be obtained by several methods. It may becalculated analytically, for the modeled body, based on the viewparameters. Additionally or alternatively, computer simulations of themodeled body and the view parameters may provide the collection ofviews. Additionally or alternatively, measurements may be performed,using a point source and a detecting unit of appropriate parameters, atdifferent locations and orientations of the detecting unit, so as tosimulate the desired geometries.

It will be appreciated that a combination of these may be used. Forexample, the measurements may be performed in air, but correctedanalytically or by computer simulations, for tissue attenuation.

Referring further to the drawings, FIGS. 9A-9F schematically illustratepossible models and collections of views, for an organ, in accordancewith embodiments of the present invention, as follows:

FIG. 9A schematically illustrates four views, formed by sectors S1, S2,S3, and S4, through the volume U, which has an even distribution ofradioactive emission.

FIG. 9B schematically illustrates three views, formed by sectors S1, S2,and S3, through the volume U, which includes a modeled pathologicalfeature, as the modeled organ target, HS.

FIG. 9C schematically illustrates three views, formed by sectors S1, S2,and to S3, through the volume U, which includes a modeled organ target,HS′, of the same type as the modeled organ target HS, (that is, either ahot region or a cold region) but somewhat displaced along the x;y;zcoordinate system. Additionally, the modeled organ target HS of FIG. 9Bis superimposed in FIG. 9C, for illustrative purposes, in order to showthe displacement delta1 between the modeled organ target HS of FIG. 9Band the modeled organ target HS′ of FIG. 9C.

FIG. 9D schematically illustrates three views, formed by sectors S1, S2,and S3, through the volume U, which includes a modeled organ target,HS″, of the same type as the modeled organ targets HS and HS′, butsomewhat displaced along the x;y;z coordinate system from them.Additionally, the modeled organ targets HS of FIG. 9B and HS′ of FIG. 9Care superimposed in FIG. 9D, for illustrative purposes, in order to showthe displacements delta2 and delta3, vis a vis HS″ of FIG. 9D.

FIG. 9E schematically illustrates three views, formed by sectors S1, S2,and S3, through the volume U, which includes two modeled organ targets,HS1 and HS2;

FIG. 9F schematically illustrates four possible models of organs, aselliptical volumes, each with a slightly different distribution ofmodeled organ targets.

The modeled organ targets may be termed emittance models. In general, anemittance model is based on a particular radiopharmaceutical, whichfixes both the rate of emission and the change in the rate of emissionwith time, determining the difference between the modeled organ targetand the background level, as a function of time. To study the effect ofdifferent radiopharmaceuticals on the views, one may provide differentemittance models, based on different radiopharmaceuticals and differentelapsed times from their administration.

The choice of an optimal set of views from among a collection of views,such as any of those illustrated in FIGS. 9A-9E, is based on a scoringfunction, which rates different sets of views in terms of theirinformation regarding the volume U, as provided by each set of views.The scoring function is based on information theoretic measures thatrate the quality of the data which each set of views provides.

A brief description of the information theoretic measures, upon whichthe scoring function may be based, is as follows:

Uniformity:

The information theoretic measure of uniformity requires that theprobability of detecting a radioactive emission from each voxel, by oneof the views, be substantially equal for all the voxels, that is,substantially uniform for all the voxels.

This is illustrated in conjunction with FIG. 9A. Basically, in one view,a voxel may have high influence on the counts that are measured, whilein another, the same voxel may have low influence on the counts that aremeasured. For example, consider a voxel u(1;1;1), in relation to theviews associated with the sectors S2 and S4. The voxel u(1;1;1) has highinfluence on the counts that are measured by the view associated withthe sector S4, but low influence on the counts that are measured by theview associated with the sector S2. The aim under uniformity is toidentify a set of views that will balance the influence of each voxelfor the entire set of views.

Separability:

The information theoretic measure of separability rates resolution, orthe ability of a set of views to distinguish between a pair of closemodels of the body structure, each having substantially identicaldimensions, so as to define substantially identical volumes U, but witha slightly different distribution of modeled organ targets.

Consider for example, a pair of models of substantially identicalvolumes, as follows: The model of FIG. 9B, which schematicallyillustrates the volume U, having the modeled organ target HS, whosecenter is at a location (x;y;z)_(HS), and the model of FIG. 9C, whichschematically illustrates the volume U, having the modeled organ targetHS′, whose center is at a location (x;y;z)_(HS). In FIG. 9C, the modeledorgan target HS of FIG. 9B is superimposed, for illustrative purposes,in order to show the displacement between the two models. Thedisplacement between the modeled organ targets is denoted as delta andmay be measured, for example, in mm. In the present example, thedisplacement between the models of FIGS. 9B and 9C is deltal, along thex-axis.

An optimal set of views, from the standpoint of separability, is thatwhich will best distinguish between HS of FIG. 9B and HS′ FIG. 9C. Thus,a score, in terms of separability is given for the pair of models, andrelates to a resolution as defined by the difference between the modelsof the pair. In the present example, the difference is deltal along thex-axis, around the locations of HS and HS′, so the score given by theinformation theoretic measure of separability, will relate specificallyto a to resolution as defined by deltal along the x-axis, around thelocations of HS and HS′. Other portions of the volume U and otherdirections may have different resolutions.

Additionally, consider the model of FIG. 9D, which schematicallyillustrates the volume U, having the modeled organ target HS″, whosecenter is at a location (x;y;z)_(HS″), wherein HS″ is displaced from HSof FIG. 9B, along the z-axis, a displacement delta2. Additionally, HS″is displaced from HS′ of FIG. 9C, along the x- and z-axes, adisplacement delta3. FIG. 9D further includes the modeled organ targetsHS of FIG. 9B and HS′ of FIG. 9C, superimposed on it, for illustrativepurposes, in order to show the displacements delta2 and delta3, vis avis HS″ of FIG. 9D.

Scores, in terms of separability, may be given to all the paringcombinations, that is the models of FIGS. 9B-9C, relating to deltal; themodels of FIGS. 9B-9D, relating to delta2, and the models of FIGS.9C-9D, relating to delta3. An optimal set of views may be selected basedon its average scores for all the pairing combinations; for example, theoptimal set may be that whose average score for all the pairingcombinations is the highest. Alternatively, a weighted average may beapplied.

It will be appreciated that where more than one modeled organ target maybe included in the volume U.

It will be further appreciated that a set of views may be selected so asto provide high resolution for portions of the volume U, known to besusceptible to pathologies, and low resolution for portions of thevolume U, known to be generally free of pathological features.

FIG. 9F schematically illustrates a pair of models of organs, aselliptical volumes, each with a slightly different distribution ofmodeled organ targets, for identifying an optimal set of views in termsof separability.

Reliability:

The information theoretic measure of reliability rates repeatability inmeasurement, so that repeated reconstructions are not substantiallydifferent. Reliability may be scored with respect to a single model of abody structure, having a specific distribution of modeled organ targets,for example, any one of the models of to FIGS. 9B-9E. Yet, preferably,several models of substantially identical volumes are provided, forexample, the four models of FIGS. 9B-9E. Substantially identical sets ofviews may be applied to all the models and be scored with respect toreliability. The optimal set is selected based on its average score forthe plurality of the models, for example, the optimal set may be thatwhose average score for the plurality of the models is the highest.

FIG. 9F schematically illustrates four models of organs, as ellipticalvolumes, each with a slightly different distribution of modeled organtargets, for identifying an optimal set of views in terms ofreliability.

A Weighted Combination:

A weighted combination of several information theoretic measures mayalso be used. For example, a plurality of models may be provided, allhaving substantially identical dimensions and volumes, as follows:

-   i. a first model of the volume U, free of modeled organ targets, as    seen in FIG. 9A, for scoring sets of views in terms of uniformity;-   ii. at least one pair of models of the volume U, with slightly    different distributions of modeled organ targets, as seen in any one    of FIGS. 9B-9C, 9B-9D, and (or) 9C-9D, for scoring sets of views in    terms of separability;-   iii. at least one model of the volume U, with a given distribution    of modeled organ targets, as seen in any one of FIGS. 9B, 9C, 9D,    and (or) 9E, for scoring sets of views in terms of reliability.

Identical sets of views may be applied to all the models of the volumeU, and each view may be scored in terms of uniformity, separability, andreliability. An optimal set of views may be selected based on asummation of the three scores, or based on a weighted average of thethree scores.

The Greedy Construction

Some approaches for selecting an optimal set are based on determining arequired quality of reconstruction, and finding a set of views thatmeets that requirement. Others are based on fixing the size for the set(i.e., the number of views in the set) and maximize the quality of thereconstruction for the given set size. Still other approaches defineboth a desired size for the set and a desired quality of toreconstruction and search for a set of the desired size, which meets thedesired quality of reconstruction.

However, given a desired size for a set of views and a desired qualityof reconstruction, while it may be possible to search through allpossible sets of the desired size, scoring each, in order to identifythe set that meets the desired quality, such a task may be monumental.For example, where the collection of views includes several thousandviews, and a set size of 100 is desired, rating each combination of 100views would be computationally impractical.

An alternative approach is the Greedy Construction. When applying theGreedy construction, an information theoretic measure is chosen, forexample, separability, and an initial set of a minimal number of viewsis defined. The set is gradually built up, so that with every addition,a view is picked so as to maximize the chosen information theoreticmeasure of the set.

This may be illustrated in conjunction with FIG. 9E. Given thatseparability is the chosen information theoretic measure, and an initialset of view S1 is defined, the additions of views S2 and S3 may then becompared in order to determine with which of them is separabilitymaximized Intuitively, for the present example, the addition of S3 willmaximize the chosen information theoretic measure of the set.

It will be appreciated that other scoring functions, as known, maysimilarly be used.

Performing Measurements

The power of the method of the present invention, of predefining a setof views based on a model of a body structure, using an informationtheoretic measure, so as to optimize the functional information from theviews of the corresponding body structure, in vivo, becomes apparentwhen compared with the prior art alternatives. The prior art relies onobtaining random views, in vivo, or views dictated by anatomicalconstraints, with no rigorous approach to the manner by which they arechosen.

The method of the present invention, of predefining a set of views,based on a model of a body structure, using an information theoreticmeasure, so as to optimize the functional information from the views ofthe corresponding body structure, in vivo, is further illustratedhereinbelow, in conjunction with FIG. 10.

Referring further to the drawings, FIG. 10 illustrates, in flowchartform, a method 320 of functional imaging, tailored for imaging fromesophagus, and optimized with respect to the functional informationgained about the body structure, by using the predefined optimal set ofviews, in accordance with embodiments of the present invention. Themethod 320 comprises:

-   in a box 322: providing a model of a body structure, based on its    geometry;-   in a box 324: providing a model of anatomical constraints, which    limit accessibility to the body structure;-   in a box 326: providing a collection of views of the modeled body    structure, obtained within the modeled anatomical constraints;-   in a box 328: providing a scoring function, by which any set of at    least one view, from a collection of views is scorable with a score    that rates information, obtained from the modeled body structure by    the set;-   in a box 330: forming sets of views from the collection of views and    scoring them, with the scoring function;-   in a box 332: selecting a set of views from the collection of views    of the modeled body structure, based on its score, as the predefined    set of views; and-   in a box 334: performing radioactive-emission measurements of an    in-vivo body structure that corresponds to the body structure that    has been modeled, selectively at the predefined set of views.

It will be appreciated that the region of interest 200 may include anorgan, such as a heart or a pancreas, a gland, such as a thyroid glandor a lymph gland, blood vessels, for example, the coronary artery or thepulmonary artery, a portion of an organ, such as an aorta or a leftatrium of a heart, a bone, a ligament, a joint, a section of the body,such as a chest or an abdomen, or a whole body.

A still more powerful approach may be achieved by taking the method ofthe present invention through second and third iterations, so as to zoomin on suspected pathological features that are identified. Specifically,when a suspected pathological feature is identified, a second, innerregion of interest, limited to the region of the pathological featureand its surrounding anatomical structure, can be identified and modeled.An optimal pathology set of views, specifically for the second, innerregion of interest, may be predefined, based on information theoreticmeasures, as before. This is illustrated hereinbelow, in conjunctionwith FIGS. 11 and 12.

Referring further to the drawings, FIG. 11 pictorially illustrates amethod 340 for zooming in on a suspected pathological feature, as aprocess of two or more iterations, in accordance with embodiments of thepresent invention, as follows:

-   In I: The region of interest 200, associated with the body structure    215, is defined for the body section 230.-   In II: The model 250 of the volume U is provided for the region of    interest 200, possibly with one or several of the modeled organ    targets HS, and within the anatomical constraints AC, for obtaining    the optimal set of views for the region of interest 200. The optimal    set of views is then applied to the body section 230.-   In III: When a suspected organ target 213 is identified, in vivo, by    radioactive-emission measurements at the optimal set of views, a    second, inner region of interest 200′ is defined, encircling the    suspected pathological feature.-   In IV: A model 250′ of a volume U′ is provided for the second, inner    region of interest 200′, preferably, with at least one modeled organ    target HS, simulating the suspected organ target 213, for obtaining    an optimal pathology set of views for the region of interest 200′.    The second, pathology set of views is then applied to the body    section 230.

Referring further to the drawings, FIG. 12 illustrates, in flowchartform, the method 340, for zooming in on a suspected pathological featureof the body structure, as a process of two iterations, in accordancewith embodiments of the present invention. The method 340 comprises:

-   in a box 342: providing a model of a body structure, based on its    geometry;-   in a box 344: providing a model of anatomical constraints, which    limit accessibility to the body structure;-   in a box 346: providing a first collection of views of the modeled    body structure, obtained within the modeled anatomical constraints;-   in a box 348: providing a first scoring function, by which any set    of at least one view, from a collection of views, is scorable with a    score that rates information, obtained from the modeled body    structure by the set;-   in a box 350: forming sets of views from the first collection of    views, and scoring them, with the first scoring function;-   in a box 352: selecting a set of views from the first collection of    views of the modeled body structure, based on its score, as the    predefined set of views;-   in a box 354: performing radioactive-emission measurements of an    in-vivo body structure that corresponds to the body structure that    has been modeled, selectively at the predefined set of views;-   in a box 356: identifying a suspected pathological feature, in the    in-vivo body structure;-   in a box 358: providing a model of the suspected pathological    feature, based on its location in the body structure and general    medical knowledge;-   in a box 360: providing a model of the anatomical constraints, which    limit accessibility to the suspected pathological feature;-   in a box 362: providing a second collection of views of the modeled    suspected pathological feature, obtained within the modeled    pathology's anatomical constraints;-   in a box 364: providing a second scoring function;-   in a box 365: forming sets of views from the second collection of    views, and scoring them, with the second scoring function;-   in a box 366: selecting a set of pathology views from the second    collection of views, based on its score, as the predefined pathology    set of views; and-   in a box 368: performing radioactive-emission measurements of the    suspected pathological feature, selectively at the predefined    pathology set of views.

It will be appreciated that the model of the suspected pathologicalfeature may be provided responsive to a patient's complaint, aphysician's examination, or based on input from another imaging system,for example, x-rays, CT, MRI, ultrasound, and gamma scanning, forexample, with a hand-held gamma camera, rather then based on thefindings of the first set of measurements, of the step 356, hereinabove.

Design of a Radioactive-Emission-Measuring Probe

While the embodiments described in conjunction with FIGS. 5A-12 relateto predefining a set of optimal views for a givenradioactive-emission-measuring to probe and a body structure, anotherside of the same coin relates to an optimal design of theradioactive-emission-measuring probe and probe system for the bodystructure, optimized with respect to functional information gained.

Thus, the embodiments described hereinbelow, in conjunction with FIGS.13A-15 illustrate methods of designing probes and probe systems,optimized with respect to information gained about a body structure.

Referring further to the drawings, FIGS. 13A-13E schematicallyillustrate possible designs of the radioactive-emission-measuring probe10, and the process of obtaining views for a given probe design, inaccordance with embodiments of the present invention.

FIGS. 13A-13C schematically illustrate theradioactive-emission-measuring probe 10 as aradioactive-emission-measuring probe 226 arranged for measuring theradioactive-emission-density distribution of three bodies, U1, U2 andU3. The volume U1 of FIG. 13A has been modeled with no modeled organtargets, in order to score the radioactive-emission-measuring probe 226in terms of uniformity. The volume U2 of FIG. 13B includes two modeledorgan targets, HS1 and HS2, and may be used for scoring theradioactive-emission-measuring probe 226 in terms of reliability. Thevolume U3 of FIG. 13C includes two modeled organ targets, HS1 and HS2′,so as to form a pair with the volume U2 of FIG. 13B, and the pair may beused for scoring the radioactive-emission-measuring probe 226 in termsof separability. Additionally, the volume U3 may be used to obtain asecond score in terms of reliability, and the two reliability scores maybe averaged. It will be appreciated that additional bodies, of differentradioactive emission density distributions may be used, for obtainingadditional scores in terms of reliability, and for forming additionalpairs, for additional scores in terms of separability, wherein thescores in terms of each scoring function may be averaged. Additionally,the scores of the three functions may be combined, for example, as asum, or as a weighted average. It will be appreciated that only one ofthe scoring functions, or only two of the scoring functions may be used.Additionally or alternatively, another scoring function or other scoringfunctions may be used.

According to the present example, the probe 226 has two detecting units222A and 222B whose collimators are arranged in parallel. The twodetecting units 222A and 222B are adapted for motion in the directionsof ±x, within the probe 226, as shown by arrows 224 and 228, so as toprovide coverage of a plane within the bodies U1 U2 and U3, in parallelsectors. Upon reaching the end of the travel in the +x direction, asshown by the arrow 224, the two detecting units 222A and 222B may berotated in the direction of ω, as shown by an arrow 217, and return inthe −x direction of the arrow 228. In this manner, complete coverage ofthe whole body is provided. A representative collection of views of theprobe 226 may be defined as a set of views of the bodies U1, U2, and U3,taken at predetermined increments of Δx and Δω.

Intuitively, a set formed of parallel sectors may score poorly in termsof uniformity since radioactive emissions from voxels closer to thedetecting unit have higher probabilities of being detected thanradioactive emissions from voxels far from the detecting unit.Additionally, a set formed of parallel sectors may score poorly in termsof separability, since it cannot distinguish between two models, whichonly differ in the depth of a pathological feature, along the z-axis.

FIG. 13D schematically illustrate the radioactive-emission-measuringprobe 10 as a radioactive-emission-measuring probe 220, arranged formeasuring the radioactive-emission-density distribution of the volumeU2, which may be used for scoring the radioactive-emission-measuringprobe 220 in terms of reliability.

The probe 220 has the two detecting units 222A and 222B, arranged tosweep a plane within the volume U2, in a windshield-wiper-like manner,along ±θ, as illustrated by arrows 216 and 218. When sweeping along ±θis completed, the detecting units 222A and 222B rotate a few degreesalong ω, as illustrated by the arrow 217, and sweeping along ±θ isrepeated in the new orientation. In this manner, coverage of the wholevolume U2 is performed, from two locations and a large plurality oforientations. A representative collection of views of the probe 220 maybe defined as a set of views of the volume U2, taken at predeterminedincrements of Δθ and Δω.

The significance of the present embodiment, is as follows:

-   i. The different detecting units 222A and 222B provide views from    different orientations; and-   ii. The different detecting units 222A and 222B may change their    view orientations.

A score may be applied to this set, based on the information theoreticmeasure of reliability.

It will be appreciated that similarly, the probe 220 may be arranged formeasuring the radioactive-emission-density distribution of the volume U1(FIG. 13A) and of the volume U3 (FIG. 13C), and possibly also of otherbodies, in order to score the radioactive-emission-measuring probe 220also in terms of uniformity and separability. The scores of the threefunctions may be combined, for example, as a sum, or as a weightedaverage. It will be appreciated that only one of the scoring functions,or only two of the scoring functions may be used. Additionally oralternatively, another scoring function or other scoring functions maybe used.

Intuitively, the set of representative collection of views of thepresent example is likely to score more highly in terms of separabilitythan that of the probe 226 of FIG. 13A, as it provides views fromdifferent locations and orientations.

In FIG. 13E the detecting units 222A and 222B of the probe 220 arefurther adapted for motion in the directions of ±x, within the probe220, as shown by the arrows 224 and 228.

Intuitively, the set of representative collection of views of thepresent example is likely to score more highly in terms of all threeinformation theoretic measures, than those of the probe of FIGS. 13A-13Cand of the probe of FIG. 13D, as the present example provides views froma large plurality of locations and orientations.

In this manner, the information theoretic measures may be used forscoring representative collections of views of suggested probe designs,and an optimal probe design may be chosen based on this score, asdescribed hereinbelow, in conjunction with FIG. 14, hereinbelow.

Referring further to the drawings, FIG. 14 illustrates, in flowchartform, a method 370 for identifying a probe optimized with respect toinformation gained about the body structure. The method 370 comprises:

-   in a box 372: providing a model of a body structure, based on its    geometry;-   in a box 374: providing a model of anatomical constraints, which    limit accessibility to the body structure;-   in a box 375: providing representative collections of views of the    modeled body structure, within the modeled anatomical constraints,    for different probe designs;-   in a box 376: providing a scoring function, by which each    representative collection of views, associated with a specific probe    design, is scorable with a score that rates information, obtained    from the body structure;-   in a box 377: scoring the representative collections of views, with    the scoring function; and-   in a box 378: selecting a probe design, based on the score of its    representative collection of views.

In this manner, a comparison of the quality of the data that may beproduced by each probe design can be made. This analysis is important atthe probe-design stage, in order to eliminate situations where viewswhich are anatomically possible and which are desired from thestandpoint of information theoretic measures, are unattainable becauseof probe design limitations. For example, the probe 190 of FIG. 4C,hereinabove, cannot be used for the windshield-wiper-like motion, shownin FIG. 13D, by the arrows 216 and 218; however, this type of coveragehas proved very valuable. Enforcing the method 370 for probe design willfavor another design.

Additionally, when selecting a probe design, it is generally desired toconsider secondary issues, such as the rate of data collection, the costof the probe, the complexity of the design, for example, in terms of thenumber of motors and motion-transfer systems, and the like.

The rate of data collection is important both because it may beassociated with patient discomfort and because it affects the number ofpatients that may be examined in a period of time. Where data collectionwith one probe design may take an hour and with another probe design itmay take 10 minutes, the design of the faster probe is highlyadvantageous. Complexity and cost are important because they affect theaccessibility of the general public to the probe.

Thus, a design scoring function may be provided, for rating each probedesign with a design score, based on any one or a combination of thesecondary issues. The design scoring function may be used for selectinga probe design from several that have been found acceptable in terms ofthe quality of the data, by the method 370 of FIG. 14.

Referring further to the drawings, FIG. 15 illustrates, in flowchartform, a method 380 of selecting a probe design, optimized with respectto information gained to about a body structure and secondary issues, inaccordance with embodiments of the present invention. The method 380comprises:

-   in a box 382: providing a model of a body structure, based on its    geometry;-   in a box 384: providing a model of anatomical constraints, which    limit accessibility to the body structure;-   in a box 385: providing representative collections of views of the    modeled body structure, within the modeled anatomical constraints,    for different probe designs;-   in a box 386: providing a scoring function, by which each    representative collection of views, associated with a specific probe    design, is scorable with a score that rates information, obtained    from the body structure;-   in a box 387: scoring the representative collections of views, with    the scoring function;-   in a box 388: identifying several probe designs as acceptable, based    on the scores of their representative collections of view;-   in a box 390: providing a design scoring function, by which each    probe design is scorable, based on the secondary issues;-   in a box 392: scoring the acceptable probe designs with a design    score;-   in a box 394: selecting a probe design, based on its design score.

It will be appreciated other manners of combining the scoring function,which rates information, and the design scoring function, which ratessecondary issues, are possible. For example, a combined scoringfunction, which takes both into account, may be used.

As will be shown, hereinbelow, in conjunction with FIGS. 19A-22H, manydifferent probe designs may provide substantially the same information,but are different in terms of their secondary considerations, that is,at different rates of data collection, different costs and differentcomplexity of their designs, for example, in terms of the number ofmotors and motion-transfer systems. Thus these may score similarly interms of functional information, and a design scoring function may beused to choose from amongst them.

Referring further to the drawings, FIGS. 16A-16L schematicallyillustrate the process of obtaining views with theradioactive-emission-measuring probe 10, to based on the model 250 ofthe volume U, in accordance with embodiments of the present invention.

The views that are obtained by the present example may be used both as:

-   i. a collection of views for the volume U, from which an optimal set    of views may be chosen, in accordance with the teachings of FIGS. 8,    10, and 12, hereinabove; and-   ii. a representative collection of views of the probe 10, in    accordance with the teachings of FIGS. 14 and 15, hereinabove.

Referring further to the drawings, FIGS. 16M-16U schematicallyillustrate experimental results obtained with theradioactive-emission-measuring probe 10, in accordance with embodimentsof the present invention.

FIGS. 16M-16O schematically illustrate line-source measurements of awire source 101 in air, with a state of the art gamma camera and withthe probes of the present invention.

As seen in FIG. 16M, the wire source 101 is Cobolt-57, of 1 mm indiameter and 200 mm in length.

FIG. 16N illustrates an image 102 of a current state of the art gammacamera (not shown), for which a value of FWHM was 12.9 mm at a measuringdistance of 10 cm from the source 101. About 5.1M counts were obtainedafter 337 seconds of counting. A 360-degree scan had been made.

FIG. 16O illustrates images 107A and 107B of the probe 10 of the presentinvention, for which values of FWHM were 7.6 mm for the image 107A and5.5 mm for the image 107B, at a measuring distance of 10 cm from thesource 101. About 11M counts were obtained after 40 seconds of counting.In other words, for a counting time of about 1/10 that of the state ofthe art camera, the number of counts was more than twice that of thestate of the art camera and the FWHM value was between 0.6 and 0.4 thatof the state of the art camera, yielding a much sharper peak.

FIGS. 16P-16R schematically illustrate line-source measurements of awire source 101, in water, with a state of the art gamma camera and withthe probes of the present invention.

As seen in FIG. 16Q, of an image 104, results of a current state of theart gamma camera (not shown) were FWHM of 15.1 mm at a measuringdistance of 15 cm from the source 101, and 1.1M counts after 337 secondsof counting.

As seen in FIG. 16O, of an image 108, results of the probe 10 of thepresent invention were FWHM of 9.2 mm, at a measuring distance of 15 cmfrom the source 101, and 2.3M counts after 40 seconds of counting.Again, for a counting time of about 1/10 that of the state of the artcamera, the number of counts were more than twice and the FWHM value wasbetween 0.6 of the state of the art camera, yielding a much sharperpeak.

FIGS. 16S and 16T schematically illustrate a Three-dimensional source,formed of two pellets 101A and 101B, in a Perspex phantom cylinder 105.The pellet 101A had a source to background ratio of 3:1 and the pellet101B had a source to background ratio of 2:1. They were arranged asshown in FIG. 16T, the distances being given in mm

A series of coronal, sagital, and transverse images were taken, by astate of the art gamma camera and by the probe of the present invention.A total of 2,500 counts were obtained, for which the state of the artcamera required 9 minutes, and the probe of the present inventionrequired 1 minute.

As seen on FIG. 16U, the state of the art camera provided littleresolution, while the probe of the present invention resolved both the3:1 source 101A and the 2:1 source 101B, as well as border artifacts andbackground rings.

EXAMPLES OF PROBE SYSTEMS

Reference is now made to the following examples ofradioactive-emission-measuring probes and probe systems, for thecomparative study taught in conjunction with FIGS. 14 and 15.

Example 1

Referring further to the drawings, FIGS. 17A-17H schematicallyillustrate detecting units 12 and blocks 90 that may be considered forpossible probe designs.

FIGS. 17A and 17B schematically illustrate side and top views,respectively, of the basic detecting unit 12 (see also FIG. 1A), havinga detector 91 and a wide-bore collimator 96, formed as a tube, of acollection angle δ1.

FIGS. 17C and 17D schematically illustrate side and top views,respectively, of the detecting unit 12, with the collimator 96 formed asa wide angle collimator, of a collection angle δ2.

FIGS. 17E and 17F schematically illustrate side and top views,respectively, of the block 90 (see also FIG. 1B) of the detecting units12, with the collimator 96 formed as a grid, and each of the detectingunit 12 having a collection angle δ3. As few as two or four, and as manyas a hundred or several hundred of the detecting units 12 may beincluded in the block 90.

FIGS. 17G and 17H schematically illustrate side and top views,respectively, of the block 90 of the detecting units 12, with thecollimator 96 formed as a grid, with two sizes of the detecting units12, as follows: small detecting units 94A, of collection angles δ4, atthe center of the grid, and large detecting units 94B, of collectionangles δ5, at the periphery. It will be appreciated that otherarrangements of detecting units of different sizes may be used.

It will be appreciated that a combination of these may be used. Forexample, the block 90 may include wide-angle collimators at theperiphery and normal collimators of 90-degrees at the center.

FIGS. 17I-17L schematically illustrate the block 90, wherein thedetector 91 is a single-pixel scintillation detector, such as NaI(Tl),LSO, GSO, CsI, CaF, or the like, operative with photomultipliers 103.

As seen in FIG. 17I, the block 90, having proximal and distal ends 109and 111, respectively, vis a vis an operator (not shown), is formed ofthe scintillation detector 91, of a single pixel, and the collimators96, to create the detecting units 12. A plurality of photomultipliers103 is associated with the single pixel scintillation detector 91, andwith proper algorithms, as known, their output can provide a twodimensional image of the scintillations in the single pixelscintillation detector 91. In essence, this is an Anger camera, asknown.

The distal view 111 of the collimator grid is seen in FIG. 17J.

Two optional proximal views 109 of the photomultipliers 103 are seen inFIGS. 17K and 17L, as a square grid arrangement, and as an arrangementof tubes.

Example 2

Referring further to the drawings, FIGS. 18A and 18B schematicallyillustrate the radioactive-emission-measuring probe 10, of the singledetecting unit 12 (see FIGS. 1A and 17A). The single detecting unit 12has a motion with respect to the housing 20, which is a combination of arotational motion around the x-axis, in the direction of ω, denoted byan arrow 44, and a translational motion along the x-axis, denoted by anarrow 46.

As a consequence, a spiral trace 48 is formed, for example, on an innersurface of a body lumen 232, as seen in FIG. 18B.

Preferably, the motions of the detecting unit 12 are contained withinthe housing 20, so that the external surface of the probe 10 remainsstationary. The external surface of the probe may be formed of a carbonfiber, a plastic, or another material, which is substantiallytransparent to nuclear radiation.

Example 3

Referring further to the drawings, FIGS. 18C and 18D schematicallyillustrate the radioactive-emission-measuring probe 10, of the singleblock 90 (FIGS. 1B and 17E). Note that all the detecting units 12 of thesingle block 90 move as a single body. The single block 90 has a motionwith respect to the housing 20, which is a combination of the rotationalmotion around the x-axis, in the direction of to, denoted by the arrow44, and the translational motion along the x-axis, denoted by the arrow46.

As a consequence, a plurality of spiral traces 49 is formed, forexample, on an inner surface of a body lumen, as seen in FIG. 18D.

Preferably, the motions of the block 90 are contained within the housing20, so that the external surface of the probe 10 remains stationary,wherein the external surface of the probe is substantially transparentto nuclear radiation.

Example 4

Referring further to the drawings, FIGS. 19A-19E schematicallyillustrate the radioactive-emission-measuring probe 10, of the singleblock 90 of a plurality of the detecting units 12.

For understanding the motion of the probe 10 of the present example, itis desirable to define a cylindrical coordinate system of a longitudinalaxis, x, and a radius r, wherein the motion around the longitudinalaxis, x, is denoted by ω, while the motion around the radius r isdenoted by φ.

The single block 90 has a motion with respect to the housing 20, whichis performed in steps, as follows:

-   i. the windshield-wiper like oscillatory motion, around the radius    r, in the direction of ±φ, as denoted by the arrow 50;-   ii. the translational motion along the x-axis, by an amount Δx, to a    new measuring position, as denoted by the arrow 46;-   iii. after traversing the length of the probe, a rotational motion    around the x-axis, in the direction of ω, by an amount Δω, as    denoted by the arrow 44, in order to perform the same measurements    at a new measuring position of ω.

As a consequence, a plurality of broken line traces 59 are formed, asseen in FIG. 19E.

Preferably, the motions of the block 90 are contained within the housing20, so that the external surface of the probe 10 remains stationary,wherein the external surface of the probe is substantially transparentto nuclear radiation.

Example 5

Referring further to the drawings, FIGS. 20A-20H schematicallyillustrate the radioactive-emission-measuring probe 10, having at leastone pair, or a plurality of pairs of blocks 90, adapted for thewindshield-wiper like oscillatory motion, around the radius r, asdenoted by the arrows 50. The oscillatory motions may be synchronized inan antipodal manner, so as to be diametrically opposed to each other, asshown in FIGS. 20B and 20E, by the arrows 54, and as shown in FIGS. 20Cand 21F by the arrows 56. It will be appreciated that the oscillatorymotions need not be synchronized in an antipodal manner. Rather, all theblocks 90 may move together, or each block 90 may move independently. Itwill be appreciated that an odd number of blocks 90 is also possible.

Additionally, a rotational motion of the housing 20, around the x-axisin the direction of ω, an amount Δω, to a new measuring position alongω, is provided, after each step of the oscillatory motion, as shown inFIG. 20D, by an arrow 52.

The resultant traces are the plurality of broken line traces 59, as seenin FIG. 20G.

In essence, the probe 10 of FIGS. 20A-20H provides views which areessentially the same as those of FIGS. 19A-19E, but in a more efficientway, since a plurality of blocks is involved.

In accordance with the present example,

-   i. The different blocks 90 provide views from different    orientations; and-   ii. The different blocks 90 may change their view orientations.

Preferably, the motions of the blocks 90 are contained within thehousing 20, so that the external surface of the probe 10 remainsstationary, wherein the external surface of the probe is substantiallytransparent to nuclear radiation.

In particular, as seen in FIG. 20H, an internal housing 21 may containall the blocks 90, so that they may be moved together by the motionprovider 76, as a single structure, while housing 20 and the externalsurface of the probe 10 remain stationary.

The operational manner of the probe 10 of FIGS. 20A-20H is described inconjunction with FIG. 23C, hereinabove.

It will be appreciated that the single detecting units 12 may be used inplace of the single blocks 90.

Example 6

Referring further to the drawings, FIGS. 21A-21D schematicallyillustrate the radioactive-emission-measuring probe 10, having at leastone pair, or a plurality of pairs of blocks 90, adapted for thewindshield-wiper like oscillatory motion, around the radius r, asdenoted by the arrow 50. The oscillatory motions are preferablysynchronized in an antipodal manner, so as to be diametrically opposedto each other, as in FIGS. 20A-20H. It will be appreciated that theoscillatory motions need not be synchronized in an antipodal manner.Rather, all the blocks 90 may move together, or each block 90 may moveindependently. It will be appreciated that an odd number of blocks 90 isalso possible.

Additionally, a rotational motion of each of the blocks 90 around thex-axis, in the direction of ω, an amount Δω, to a new measuring positionalong ω, is provided, after each step of the oscillatory motion, asshown in FIG. 21B, by the arrows 44.

This is unlike FIG. 20D, wherein the internal housing 21 moved as asingle unit, as shown in FIGS. 20D and 20H.

The resultant traces are the plurality of broken line traces 59, as seenin FIG. 21D. In essence, the probe 10 of FIGS. 21A-21D provides viewswhich are essentially the same as those of FIGS. 19A-19E, and of FIGS.20A-20H, but in a different manner.

In accordance with the present example,

-   i. The different blocks 90 provide views from different    orientations; and-   ii. The different blocks 90 may change their view orientations.

Preferably, the motions of the blocks 90 are contained within thehousing 20, so that the external surface of the probe 10 remainsstationary, wherein the external surface of the probe is substantiallytransparent to nuclear radiation.

It will be appreciated that the detecting units 12 may be used in placeof the blocks 90.

Example 7

Referring further to the drawings, FIGS. 22A-22H schematicallyillustrate a radioactive-emission-measuring probe 95, comprising aplurality of assemblies 92, each assembly 92 being similar inconstruction to the probe 10 of FIG. 20H, in accordance with embodimentsof the present invention.

The plurality of assemblies 92 are preferably arranged in parallel, andtheir rotational motions, around the x-axis, may be synchronized in anantipodal manner, so as to be diametrically opposed to each other, asshown in FIG. 22C, by arrows 62, and in FIG. 22G, by arrows 64. It willbe appreciated that the rotational motion around the x-axis need not besynchronized in an antipodal manner, and may be performed in parallel,or independently.

Thus, the resultant traces are a large plurality of the broken linetraces 66 and 68, as seen in FIGS. 22D and 22H.

In essence, the probe 95 of FIGS. 22A-22H provides views which areessentially the same as those of FIGS. 19A-19E, 20A-20H, and 21A-21D,but far more efficiently, since a plurality of assemblies are involved.

In accordance with the present example,

-   i. The different blocks 90 provide views from different    orientations;-   ii. The different blocks 90 may change their view orientations;-   iii. The different assemblies 92 provide views from different    orientations; and-   iv. The different assemblies 92 may change their view orientations.

The operational manner of the probe 95 is described in conjunction withFIG. 23D, hereinbelow, for the at least two assemblies 92A and 92B.

Preferably, the motions of the blocks 90 and of the assemblies 92 arecontained within the housing 20, so that the external surface of theprobe 95 remains stationary, wherein the external surface of the probe95 is substantially transparent to nuclear radiation.

It will be appreciated that probe 95 may include a plurality ofassemblies 92, which are not parallel to each other. For example, theassemblies 92 may be at right angles to each other, or at some otherangle.

It will be appreciated that the assemblies 92 may include the detectingunits 12 rather then the blocks 90.

Example 8

Having designed a radioactive-emission-measuring probe capable ofobtaining a collection of views, and having predefined a set of views,which is optimal for a body structure, based on its model, the task ofperforming measurements, selectively at the predefined set of views,would be quite impossible if it were to be performed manually.Generally, between several hundreds and several thousands of views aretaken, and manually tuning each to a predetermined location,orientation, and possibly also duration would be impractical. Therefore,the probe and method of the present invention are operative with anoverall system, in which computer controlled motion providers govern themotions of the detecting units or of the overall probe. The computer maybe any one of a personal computer, a laptop, a palmtop, or anothercomputer, adapted for communication with the probe, or a microcomputer,built into the probe. Additionally, a combination of a microcomputer,built into the probe, and an external computer such as a personalcomputer, a laptop, a palmtop, or the like, may be used.

Preferably, before measurements are performed, personal details are fedinto the computer, and the models of the body structure and anatomicalconstraints are adapted to these details. The personal details mayinclude age, sex, weight, body type, and the like.

Referring further to the drawings, FIGS. 23A-23D schematicallyillustrate radioactive-emission-measuring-probe systems 400 inaccordance with embodiments of the present invention.

As seen in FIG. 23A, the probe system 400 includes the probe 10, havinga controller 404, in communication with one or several motion providers76, for sending signals of views' locations and orientations to the oneor several motion providers 76. The one or several motion providers 76,in turn, govern the motions of one or several of the detecting units 12.The one or several of the detecting units 12 collect the measurements atthe predefined locations and orientations and communicate the data tothe controller 404. Signals of new locations and orientations are thencommunicated by the controller 404 to the one or several motionproviders 76. Each of the motion providers 76 may control the motion ofone of the detecting units 12 or of a plurality of the detecting units12.

Preferably, the controller 404 registers the location and orientation ofeach of the detecting unit 12 as it moves. Additionally oralternatively, a position-tracking device may be associated with each ofthe detecting units 12.

Preferably, a position-tracking device 418 is associated with the probe10 as a whole, for registering its position with respect to the body,for example, with respect to the body structure 215 (FIG. 5A).

A power supply 410 powers the probe 10. Alternatively, power may besupplied from the grid.

Preferably, a transceiver 402, or a transmitter 402, reports themeasurements to an external computer. Alternatively, a cable may beused. Alternatively, the controller 404 includes a microcomputer, or thelike, and performs the data analysis.

Additionally, the transceiver 402 may be adapted to receive input datarelating to the personal details of the patient, such as the age, sex,weight, body type, and the like, in order to adjust the model of thebody structure, hence the locations and orientations of the predefined,optimal set of views, to the particular patient.

Furthermore, the transceiver 402 may be adapted to receive input datafrom an ultrasound imager, for providing information such as location,size of the body structure and the like, by ultrasound imaging, in orderto adjust the model of the body structure, hence the locations andorientations of the predefined, optimal set of views, to the particularpatient.

Preferably, the motion of the one or several motion providers 76 relatesto motion of the detecting units 12 with respect to the probe housing20, for example, as to taught in conjunction with FIG. 13E, by themotion of detecting units 222A and 222B, with respect to the housing220, as shown by the arrows 216 and 218.

Alternatively or additionally, the motion of the one or several motionproviders 76 may relate to motion of the probe housing as a whole, withrespect to the body structure 215 (FIG. 5A), for example, as taught inconjunction with FIG. 13E, by the motion the probe 220, as shown by thearrows 217 and 228.

It will be appreciated that the controller 404, while being part of thesystem 400, need not part of the actual probe 10. Rather it may be anexternal computer, communicating with the probe 10 either by cables orvia a transceiver.

As seen in FIG. 23B, the probe 10 includes the blocks 90, eachcomprising a plurality of the detecting units 12, each block 90 movingas a single body.

As seen in FIG. 23C, the individual motion of the blocks 90 is governedby a secondary motion provider 78. Additionally, all of the blocks 90form an assembly 92, which moves by the motion provider 76, for example,within an internal housing 21, as illustrated hereinbelow in conjunctionwith FIG. 20H. For example, the secondary motion provider 78 may providethe motion described by the arrows 50 of FIGS. 20B and 20C or 20F and20F, hereinbelow while the motion provider 76 may provide the motiondescribed by the arrow 52 of FIG. 20H, hereinbelow.

It will be appreciated that the multiple motions may be provided to thedetecting units 12, rather then to the blocks 90.

It will be appreciated that a tertiary motion provider may also be usedand that many arrangements for providing the motions are possible, andknown.

As seen in FIG. 23D, at least two assemblies 92 may be provided, eachwith a dedicated motion provider 76 and a dedicated secondary motionprovider 78. It will be appreciated that the multiple motions may beprovided to the detecting units 12, rather then to the blocks 90. Itwill be appreciated that tertiary motion providers may also be used andthat many arrangements for providing the motions are possible, andknown.

In the example of FIG. 23D, the controller 404, while being part of thesystem 400, is not part of the actual probe 10. For example, it may bean external computer, communicating with the probe 10 either by cablesor via a transceiver.

Examples of Probe Systems for Specific Applications

Reference is now made to the following examples ofradioactive-emission-measuring probes and probe systems, for specificapplications.

Example 9

Referring further to the drawings, FIGS. 24A-32 schematically illustratethe radioactive-emission-measuring probe 10, for the prostate, inaccordance with an embodiment of the present invention.

FIGS. 24A-24C schematically illustrate the modeling of a prostate and alocation of a pathology, as a process of two iterations, for zooming inon the pathology, in accordance with embodiments of the presentinvention.

FIG. 24A schematically illustrates a body section 230, which includes aprostate 260, which has sections 262, 264 and 266, and a pathology 265in section 264. Additionally, the body section 230 includes a rectum268, from which the prostate 260 may be viewed.

FIG. 24B schematically illustrates the model 200 of the body section230, including the prostate 260, of sections 262, 264 and 266, and therectum 268. An optimal set of views is predefined based on the model 200and a first scoring function. The first scoring function may be based onregions of interest similar to the pathology 265, as known, from medicalrecords of common pathologies. Measurements of radioactive emission arethen taken at the predefined views, in vivo, for the prostate 260.

As seen in FIG. 24C, upon discovering the pathology 265, by the in-vivomeasurements, a second model 250 of the section 264 is made, for zoomingin on the pathology 265, and a second optimal set of views ispredefined, based on the second model 250 of the section 264 and asecond scoring function, for zooming in on the pathology 265.Measurements of radioactive emission are then taken at the predefinedsecond set of views, in vivo, for the section 264 and the pathology 265.

It will be appreciated that the first and second scoring functions maybe based on any one of or a combination of the information theoreticmeasures of uniformity, separability, and reliability. It will befurther appreciated that the first and second scoring functions need notbe the same.

FIGS. 25A-25E illustrate an external appearance and an internalstructure, of the probe 10. The radioactive-emission-measuring probe 10for the prostate has an extracorporeal portion 80 and an intracorporealportion 82, which is adapted for insertion to a rectum. The housing 20of the intracorporeal potion 82 is preferably shaped generally as acylinder and defines a longitudinal axis along the x axis, and a radius,perpendicular to the longitudinal axis. The intracorporeal portion 82preferably includes two pairs of assemblies 90, arranged in the housing20. It will be appreciated that another number of assemblies, forexample, a single pair, or three pairs, is similarly possible. An oddnumber of assemblies is similarly possible. In essence, the probe 10 ofthe present example is analogous to the probe 10 of FIG. 23C and FIGS.20A-20H, and particularly, to FIG. 20H. The rotational motion, in thedirection of the arrow 52 of FIG. 20H, is provided by a motor 88 (FIG.25C) and a main shaft 85. The motor 88 may be an electric motor, forexample, a servo motor. The motor 88 and main shaft 85, together, form amotion provider 76 for the rotational motion in the direction of thearrow 52 of FIG. 20H. The oscillatory motion, in the direction of thearrows 50 of FIGS. 20B-20C and 20E-20F, is provided by a secondary motor86, a secondary shaft 84 and a motion transfer link 74. The secondarymotor 86 may also be an electric motor, for example, a servo motor. Thesecondary motor 86, secondary shaft 84 and the motion transfer link 74,together, form the secondary motion provider 78, in the direction of thearrows 50 of FIGS. 20A-20H.

The significance of the present embodiment, is as follows:

-   i. The different assemblies 90 provide views from different    orientations; and-   ii. The different assemblies 90 may change their view orientations    independent of each other.

It is important to point out that during the operation of the probe 10,the external surface of the intracorporeal portion 82 (FIG. 25D-25E)remains stationary, while the inner housing 21 (FIG. 25C) rotates aroundthe x axis. The external surface of the intracorporeal portion 82 may beformed of a carbon fiber, a plastic, or another material, which issubstantially transparent to nuclear radiation.

FIG. 25E illustrates further the internal structure of theradioactive-emission-measuring probe for the prostate, in accordancewith an embodiment of the present invention, showing the assemblies 90within the housing 20. Each assembly may be a single detecting unit 12,or a plurality of the detecting units 12, for example, 36 of thedetecting units 12, for example, as an array of 6×6, or 99 of thedetecting units 12, for example, as an array of 11×9, or another numberof the detecting units 12, arranged as an array or arranged in anothergeometry.

Referring further to the drawings, FIG. 26 illustrates further theinternal structure of the radioactive-emission-measuring probe for theprostate, in accordance to with an embodiment of the present invention,showing the oscillatory motion (in the direction of the arrows 50 ofFIGS. 20A, and 20C) of the assemblies 90 within the housing 20.

FIGS. 27-30C schematically illustrate the radioactive-emission-measuringprobe 10, for the prostate, in accordance with another embodiment of thepresent invention. In accordance with the present embodiment, the probe10 further includes an ultrasound transducer 85, arranged, for example,at the tip of the intracorporeal portion 82.

FIG. 27 illustrates the external appearance of the probe 10 with theultrasound transducer 85 at its tip.

FIG. 28 illustrates the ultrasound wave 87, impinging on the prostate260.

FIGS. 29A-29C illustrate the fusing of a radioactive-emission image andan ultrasound image, to illustrate the functional information of theradioactive-emission image with the structural information of theultrasound image. The ultrasound image is seen in FIG. 29A, theradioactive-emission image is seen in FIG. 29B, and the fusing of thetwo is seen in FIG. 29C.

FIGS. 30-32 schematically illustrate the radioactive-emission-measuringprobe 10, for the prostate, in accordance with another embodiment of thepresent invention. In accordance with the present embodiment, the probe10 further includes an ultrasound transducer 85, and a surgical needle83, in a needle guide 31, arranged alongside the probe 10, for obtaininga biopsy or for other minimally invasive procedures.

FIG. 30 schematically illustrates the surgical needle 81 as itpenetrates the prostate 260 from the rectum 268.

FIGS. 31 and 32 schematically illustrate the manner of guiding theneedle 31. A track 89 shows the surgeon the direction of the needle,while the probe 10 produces the functional image of the pathology 265 inthe prostate 260. By moving the probe 10, manually, the surgeon canalign the track 89 with the pathology 265, as shown in FIG. 32. Oncealigned, he can eject the needle 83, as shown in FIG. 30.

Example 10

Referring further to the drawings, FIG. 33 pictorially illustrates themethod 340 for zooming in on a suspected pathological feature in awoman's reproductive system, as a process of two or more iterations, inaccordance with embodiments of the present invention, as follows:

As seen in FIG. 33, the method 340 may be described, pictorially, asfollows:

-   In I: The region of interest 200, associated with the woman's    reproductive system 215, is defined for the body section 230.-   In II: The model 250 of the volume U, is provided for the region of    interest 200, possibly with one or several of the modeled organ    targets HS, and within the anatomical constraints AC, for obtaining    the optimal set of views for the region of interest 200. The optimal    set of views is then applied to the body section 230.-   In III: When a suspected organ target 213 is identified, in vivo, by    radioactive-emission measurements at the optimal set of views, a    second, inner region of interest 200′ is defined, encircling the    suspected pathological feature.-   In IV: A model 250′ of a volume U′ is provided for the second, inner    region of interest 200′, preferably, with at least one modeled organ    target HS, simulating the suspected organ target 213, for obtaining    an optimal pathology set of views for the region of interest 200′.    The second, pathology set of views is then applied to the body    section 230.

Referring further to the drawings, FIGS. 34A-34R schematicallyillustrate radioactive-emission measuring probes 600, tailored forimaging the woman's reproductive system and optimized with respect tothe functional information gained, regarding the body structures of thewoman's reproductive system, such as the cervix 274, the uterus 276, theovaries 278, and the fallopian tubes 280, in accordance with preferredembodiments of the present invention.

FIG. 34A schematically illustrates the basic radioactive-emissionmeasuring probe 600, for a body lumen, for example, the vagina 272, thecervix 274, the uterus 276, the rectum 292, or the sigmoid colon 294.The probe 600 includes an to extracorporeal portion 610, whichpreferably comprises a control unit, and an intracorporeal portion 630,having proximal and distal ends 631 and 633, with respect to an operator(not shown).

The control unit of the extracorporeal portion 610 may include controlbuttons 612 and possibly a display screen 614, and may provideconnections with a computer station. It may receive power from a grid orbe battery operated. The control unit of the extracorporeal portion 610may further include a computer or a microcomputer. It will beappreciated that the control unit may be incorporated with theintracorporeal section 630, and operated remotely.

The intracorporeal portion 630 defines a cylindrical coordinate systemof x;r, wherein x is the longitudinal axis. The plurality of blocks 90along the length of the intracorporeal portion 630 is housed in an innerhousing 21 (FIG. 20H).

Each of the blocks 90 is adapted for the windshield-wiper likeoscillatory motion, around the radius r, as denoted by the arrows 50.The oscillatory motions may be synchronized in an antipodal manner, soas to be diametrically opposed to each other, as shown hereinabove inFIGS. 20B and 20E, by the arrows 54, and as shown hereinabove in FIGS.20C and 20F by the arrows 56. However, other motions are also possible.For example, the blocks 90 may move together, or independently. It willbe appreciated that an odd number of blocks 90 is also possible.

Additionally, the inner housing 21 is adapted for rotational motionaround the x-axis, in the direction of ω, wherein after each step ofoscillatory motion at a certain orientation of ω, the inner housingrotates by a step to a new orientation of ω, and the oscillatory motionis repeated.

As a consequence, a plurality of broken line traces 59 are formed, inthe body section 230, as seen in FIG. 34J.

Preferably, the controller or the computer registers the locations andorientations of each detecting unit or block and correlates themeasurements with the corresponding positions and orientations.

A position-tracking device 635 may also be used, for providinginformation regarding the position of the probe 600 relative to a knownreference. For example, if a structural scan, or another scan by anotherimager has been made, the position-tracking device 635 may be used toregister the previous scan with the measurements of the probe 600.

It will be appreciated that the probe 600 may include detecting units 12rather then blocks 90.

Preferably, the housing 20 remains stationary and is substantiallytransparent to nuclear radiation, formed, for example, of a hydrocarbonmaterial.

The intracorporeal portion 630 may further include dedicated electronics634 and motion providers 636, such as miniature motors and motiontransfer systems, as known.

FIGS. 34B and 34C schematically illustrate side and distal views,respectively, of the radioactive-emission measuring probe 600, having anultrasound imager 640 at its distal tip 633. The ultrasound imager 640may provide a structural image which may be correlated with thefunctional image. Additionally, it may be used for providing the sizeand location of the body structure for modeling. Furthermore, it may beused for providing attenuation correction to the radioactive emissionmeasurements.

FIGS. 34D and 34E schematically illustrate side and distal views,respectively, of the radioactive-emission measuring probe 600, having anMRI imager 642 at its distal tip 633. The MRI imager 642 may provide astructural image which may be correlated with the functional image.Additionally, it may be used for providing the size and location of thebody structure for modeling. Furthermore, it may be used for providingattenuation correction to the radioactive emission measurements.

FIGS. 34F-34I schematically illustrate the radioactive-emissionmeasuring probe 600, having a distal block 90A at its distal tip 633.The distal block 90A at the distal tip is also adapted for oscillatorymotion, but about the x-axis, as seen by an arrow 53. When combined withthe rotational motion around the x-axis, it produces traces 55 in theshape of a star, in the body section 230, as seen in FIG. 34K.

It will be appreciated that a single distal detecting unit may beemployed in place of the distal block 90A.

FIGS. 34L-34Q schematically illustrates the radioactive-emissionmeasuring probe 600, for a body lumen, having the distal block 90A atits distal tip 633, adapted for a deployed and a retracted position, andfor oscillatory motion about the x-axis, when deployed. The probe 600further has the ultrasound imager 640 at its distal tip 633, as a ring,similarly having a deployed and a retracted position.

FIGS. 34N-34P illustrate the distal block 90A deployed, and theultrasound imager 640 retracted. In this manner, the ultrasound imager640 does not obstruct the oscillatory motion of the distal block 90A atthe distal tip 633.

FIG. 34Q illustrates the distal block 90A retracted and the ultrasoundimager deployed so the distal block 90A does not obstruct the view ofthe ultrasound imager. It will be appreciated that the ultrasound imageis to be taken once, from the distal tip 633, while theradioactive-emission measurements are to be taken at a plurality oforientations, from the distal tip 633.

FIG. 34R illustrates the probe 600 with a cable 620 connecting theintracorporeal portion 630 and the extracorporeal portion 610, forexample, for imaging the ovaries and the fallopian tubes from thesigmoid colon.

It will be appreciated that the probes 600 of the present invention mayalso be moved manually, both linearly, into the body lumen androtationally, around its longitudinal axis, preferably while theposition-tracking device 635 (FIG. 34A) registers its position.

It will be appreciated that a probe with a single block or a singledetecting unit may also be used.

Example 11

Referring further to the drawings, FIGS. 35A-35Q schematicallyillustrate radioactive-emission measuring probes 600, adapted for theesophagus, in accordance with preferred embodiments of the presentinvention.

FIG. 35A schematically illustrates the basic radioactive-emissionmeasuring probe 600, for the esophagus. The probe 600 includes anextracorporeal portion 610, which comprises a control unit, and anintracorporeal portion 630, having proximal and distal ends 631 and 633,with respect to an operator (not shown). A flexible cable 620 connectsbetween them.

The control unit 610 may include control buttons 612 and possibly adisplay screen 614, and may provide connections with a computer station.It may receive power from a grid or be battery operated. The controlunit 610 may further include a computer or a microcomputer.

The intracorporeal portion 630 is constructed essentially as the probe10 of FIG. 23C and FIGS. 20A-20H, and specifically, FIG. 20H.

Thus, the intracorporeal section 630 defines a cylindrical coordinatesystem of x;r, wherein x is the longitudinal axis. The plurality ofblocks 90 along the intracorporeal portion 630 is housed in an innerhousing 21.

Each of the blocks 90 is adapted for the windshield-wiper likeoscillatory motion, around the radius r, as denoted by the arrows 50.The oscillatory motions may be synchronized in an antipodal manner, soas to be diametrically opposed to each other, as shown hereinabove inFIGS. 20B and 20E, by the arrows 54, and as shown hereinabove in FIGS.20C and 20F by the arrows 56. However, other motions are also possible.For example, the blocks 90 may move together, or independently. It willbe appreciated that an odd number of blocks 90 is also possible.

Additionally, the inner housing 21 is adapted for rotational motionaround the x-axis, in the direction of ω, wherein after each step ofoscillatory motion at a certain orientation of ω, the inner housingrotates by a step to a new orientation of ω, and the oscillatory motionis repeated.

As a consequence, a plurality of broken line traces 59 are formed, inthe body section 230, as seen in FIG. 35J.

Preferably, the controller or the computer registers the locations andorientations of each detecting unit or block and correlates themeasurements with the corresponding positions and orientations.

A position-tracking device 635 may also be used, for providinginformation regarding the position of the probe relative to a knownreference.

It will be appreciated that the probe 600 may include detecting units 12rather then blocks 90, for example, as taught in conjunction with FIGS.20A-20G.

Preferably, the housing 20 remains stationary, and has an externalsurface, which is substantially transparent to nuclear radiation.

A ball bearing 632 may be used at the connecting point with the cable620, to enable the rotational motion.

The intracorporeal section 630 may further include dedicated electronics634 and motion providers 636, such as miniature motors and motiontransfer systems, as known. Alternatively, the motion may be transferredvia the cable 620.

FIGS. 35B and 35C schematically illustrate side and distal views,respectively, of the radioactive-emission measuring probe 600, for theesophagus, having an ultrasound imager 640 at its distal tip 633. Theultrasound imager 640 may provide a structural image which may becorrelated with the functional image. Additionally, it may be used forproviding the size and location of the relevant organ for modeling.Furthermore, it may be used for providing attenuation correction to theradioactive emission measurements.

FIGS. 35D and 35E schematically illustrate side and distal views,respectively, of the radioactive-emission measuring probe 600, for theesophagus, having an MRI imager 642 at its distal tip 633. The MRIimager 642 may provide a structural image which may be correlated withthe functional image. Additionally, it may be used for providing thesize and location of the relevant organ for modeling. Furthermore, itmay be used for providing attenuation correction to the radioactiveemission measurements.

FIGS. 35F-35I schematically illustrate the radioactive-emissionmeasuring probe 600, for the esophagus, having a block 90 at its distaltip 633. The block 90 at the distal tip is also adapted for oscillatorymotion, but about the x-axis, as seen by an arrow 53. When combined withthe rotational motion around the x-axis, it produces traces 55 in theshape of a star, in the body section 230, as seen in FIG. 35K.

FIGS. 35L-35Q schematically illustrates the radioactive-emissionmeasuring probe 600, for the esophagus, having a block 90 at its distaltip 633, adapted for a deployed and a retracted position, and foroscillatory motion about the x-axis, when deployed. The probe 600further has the ultrasound imager 640 at its distal tip 633, as a ring,similarly having a deployed and a retracted position.

FIGS. 35N-35P illustrate the block 90 deployed, and the ultrasoundimager 640 retracted. In this manner, the ultrasound imager 640 does notobstruct the oscillatory motion of the block 90 at the distal tip 633.

FIG. 35Q illustrates the block 90 retracted and the ultrasound imagerdeployed so the block 90 does not obstruct the view of the ultrasoundimager. It will be appreciated that the ultrasound image is to be takenonce, from the distal tip 633, while the radioactive-emissionmeasurements are to be taken at a plurality of orientations, from thedistal tip 633.

FIG. 35R schematically illustrates the body section 230, showing anesophagus 650 and nearby organs, such as the heart 660 and the lungs658.

FIG. 35S schematically illustrates the body section 230, showing thestomach 662, and nearby organs, such as the pancreas 664, and the liver666.

The radioactive-emission measuring probe 600 for the esophagus (FIGS.35A-35Q), is adapted for oral insertion, through a mouth 652, and isfurther designed for identifying pathological features in a neck area654, for example, as relating to the vocal cords, the thyroid glands,the submandibular glands. Additionally, it is designed for identifyingpathological features in the trachea 656, the lungs 658, the heart 660,the breasts, the stomach 662, the pancreas 664, and the liver 666, aswell as other relevant organs and glands, for example, the lymph glands.

The probe system of the present invention allows imaging of internalorgans from a close proximity. Additionally, it is particularlyadvantageous for overweight people and for women with large breasts, forwhom extracorporeal imaging, for example, extracorporeal cardiac imagingby nuclear emission measurements, is ineffective, because of losses inthe tissue.

For cardiac imaging, the radiopharmaceuticals associated with the probeof FIGS. 35A-35Q may be Myoview™ (technetium Tc-99m tetrofosmin), acardiac imaging agent, of GE Healthcare, GE Medical Systems,http://www.gehealthcare.com/contact/contact_details.html#diothers.Alternatively, it may be Cardiolite (Sestamibi radilabeled with TC99),of DuPont,http://www1.dupont.com/NASApp/dupontglobal/corp/index.jsp?page=/content/US/en_US/contactus.html.It will be appreciated that other agents may be used, as known, forother relevant organs, for example, for the detection of canceroustissue or other pathologies.

Example 12

Referring further to the drawings, FIGS. 36A-36C schematicallyillustrate the body section 230, as a heart, which includes the regionof interest 200, associated with the organ 215, being the heart 215. Theheart 215 includes an aorta 242, a left atrium 244 and a right atrium246.

FIG. 36B schematically illustrates a second, inner region of interest200′, associated with the aorta 242.

Similarly, FIG. 36C schematically illustrates a second, inner region ofinterest 200′, associated with the left atrium 244.

Referring further to the drawings, FIGS. 37A-43E schematicallyillustrate a cardiac probe system 500, in accordance with a preferredembodiment of the present invention.

FIGS. 37A-37D schematically illustrate the basic components of thecardiac probe system 500, in accordance with embodiments of the presentinvention. These include an operator computer station 510, a chair 520,and a radioactive-emission-measuring probe assembly 530.

As seen in FIG. 37D, computer station 510 may be further adapted forinput of an ultrasound imager 535, for example, a handheld ultrasoundimager 535, possibly with a position-tracking device 537, or a 3-Dultrasound imager. The data provided by the ultrasound imager 535 may beused in the modeling of the heart. Preferably, the data of theultrasound imager may be co-registered with the radioactive emissionmeasurements, on the same frame of reference, for providingco-registration of structural and functional imaging. It will beappreciated that the imager 535 may be an MRI imager.

FIG. 38 schematically illustrates the chair 520 and the probe assembly530, arranged for operation, in accordance with a preferred embodimentof the present invention. Preferably, the chair 520 is in a partialreclining position, and the probe assembly 530 is designed to comeagainst it, opposite the chest of a person, when sitting on the chair520. Preferably, the probe assembly 530 includes a housing, which issubstantially transparent to radioactive emission. Alternatively, nohousing, or a housing which is open on the side facing a patient may beused.

It will be appreciated that another chair or a bed may be used ratherthan the chair 520. Alternatively, the patient may be standing.

FIGS. 39A-39B schematically illustrate possible inner structures of theprobe assembly, in accordance with preferred embodiments of the presentinvention.

FIG. 39A schematically illustrates the inner structure of the probeassembly 530, showing the housing 20, the parallel lines of assemblies92, possibly of an even number, each with a dedicated motion provider 76and a dedicated secondary motion to provider 78, and the rows of blocks90, possibly arranged in pairs, along the assemblies 92.

The probe assembly 530 defines an internal frame of reference 80, whileeach assembly 92 has a reference cylindrical coordinate system of x;r,with rotation around x denoted by ω and rotation around r denoted by φ,wherein the oscillatory motion about r is denoted by the arrow 50.

Preferably, the motion of the probe assembly 530 corresponds to thatdescribed hereinabove, in conjunction with FIGS. 20A-20H and 22A-22H, asfollows:

The plurality of blocks 90 is adapted for the windshield-wiper likeoscillatory motion, around the radius r, as denoted by the arrow 50. Theoscillatory motions may be synchronized in an antipodal manner, so as tobe diametrically opposed to each other, as shown hereinabove in FIGS.20B and 20E, by the arrows 54, and as shown hereinabove in FIGS. 20C and20F by the arrows 56. However, other motions are also possible. Forexample, the blocks 90 may move together, or independently. It will beappreciated that an odd number of blocks 90 is also possible.

Furthermore, the plurality of assemblies 92 are preferably arranged inparallel, and their rotational motions, around the x-axis, in thedirection of to, may also be synchronized in an antipodal manner, so asto be diametrically opposed to each other, as shown hereinabove, in FIG.22C, by arrows 62, and as shown hereinabove in FIG. 22G, by arrows 64.However, other motions are also possible. For example, the assemblies 92may move together, or independently. It will be appreciated that an oddnumber of assemblies 92 is also possible.

Thus, the resultant traces are a large plurality of the broken linetraces 59, as seen hereinabove, in conjunction with FIGS. 22D and 22H,on the chest of the patient.

In accordance with the present example,

-   i. The different blocks 90 provide views from different    orientations;-   ii. The different blocks 90 may change their view orientations;-   iii. The different assemblies 92 provide views from different    orientations; and-   iv. The different assemblies 92 may change their view orientations.

The operational manner of the probe 530 is described hereinbelow inconjunction with FIG. 23D, for the at least two assemblies 92.

Preferably, the motions of the blocks 90 and of the assemblies 92 arecontained within the housing 20, so that the external surface of theprobe assembly 530 remains stationary, wherein the external surface ofthe probe assembly 530 is substantially transparent to nuclearradiation. Alternatively, the housing may be open on the side facing thepatient.

It will be appreciated that the oscillatory motions need not besynchronized in an antipodal manner. Rather, the blocks 90 may movetogether, or independently. It will be appreciated that an odd number ofblocks 90 is also possible.

It will be appreciated that probe 530 may include a plurality ofassemblies 92, which are not parallel to each other. For example, theassemblies 92 may be at right angles to each other, or at some otherangle. It will be appreciated that the assemblies 92 may includedetecting units 12 rather then blocks 90, for example, as in the probe10 of FIGS. 20A-20G.

FIG. 39B schematically illustrates a section 531 of the probe assembly530, showing the inner structure thereof, in accordance with anotherembodiment of the present invention. Accordingly, the probe assembly 530may include the housing 20, and a single one of the assemblies 92,within the housing 20, having the dedicated motion provider 76, thededicated secondary motion provider 78, and the rows of blocks 90.Additionally, in accordance with the present embodiment, the probeassembly 530 includes a tertiary motion provider 77, for sliding theassembly 90 laterally, in the directions of the arrow 75, along thechest of the patient (not shown). In this manner, imaging of the chestmay be performed with the single assembly 92.

FIGS. 40A and 40B schematically illustrate the assembly 92 and the block90, in accordance with a preferred embodiment of the present invention.In essence, the assembly 92 is constructed in a manner similar to theprobe 10 of FIGS. 20A-20H, and specifically FIG. 20H, and according toFIG. 23D, hereinabove.

Thus the assembly 92 includes a row of at least two blocks 90, eachadapted of oscillatory motion about r. The blocks 90 are arranged withinthe inner housing 21.

A motor 88 and a shaft 85 form the motion provider 76, while a secondarymotor 86 and a secondary shaft 84 form the secondary motion provider 78,for the oscillatory motion about r. A plurality of motion transfersystems 74, for example to gear systems, equal in number to the numberof blocks 90, transfer the motion of the secondary motion provider 78 tothe blocks 90. The motion transfer systems 74, of gears, make itpossible to provide the row of blocks 90 with any one of paralleloscillatory motion, antipodal oscillatory motion, or independent motion,depending on the gear systems associated with each block 90. It will beappreciated that other motion transfer systems, as known, may be used.

It will be appreciated that detecting units 12 may be used in place ofblocks 90.

In accordance with the present example, adjacent blocks 90A and 90B maymove in an antipodal manner and adjacent blocks 90C and 90D may move inan antipodal manner, while adjacent blocks 90B and 90C may move inparallel. It will be appreciated that many other arrangements aresimilarly possible. For example, all the pairing combinations of theblocks 90 may move in an antipodal manner, all the blocks 90 may move inparallel, or the blocks 90 may move independently. It will beappreciated that an odd number of blocks 90 may be used in the assembly92.

FIG. 41 schematically illustrates the block 90, in accordance with apreferred embodiment of the present invention. The block 90 includes aframe 93, which houses the detector material 91, which is preferablypixilated, and the collimators 96. Additionally, the frame 93 housesdedicated electronics 97, preferably on a PCB board 99. Furthermore,where several modules of the detector material 91 need to be used, astructural element 89 may be provided to hold the different modules ofthe detector material 91 together. It will be appreciated that a singlepixel detector may be used. Alternatively, a single module of apixilated detector may be used. Alternatively, the block 90 may beconstructed as any of the examples taught in conjunction with FIGS.17A-17L, or as another block, as known.

The dimensions, which are provided in FIG. 41, are in mm. It will beappreciated that other dimensions, which may be larger or smaller, maysimilarly be used.

FIG. 42 schematically illustrates the cardiac model 250, in accordancewith a preferred embodiment of the present invention. The cardiac model250 includes the volume U, for example, as a cylinder, and theanatomical constraints AC. The rows of blocks 90 are arranged around thevolume U, as permissible by the anatomical constraints AC.

FIGS. 43A-43E schematically illustrate the blocks 90, arranged forviewing the cardiac model 250, in accordance with a preferred embodimentof the present invention.

In FIG. 43A, the block 90 is shown with the frame 93, which houses thedetector material 91, which is preferably pixilated, and the collimators96. Additionally, the frame 93 houses the dedicated electronics 97, onthe PCB board 99.

In FIG. 43A, fields of view 98 of the blocks 90 are seen for a situationwherein adjacent blocks 90A and 90B move in an antipodal manner, whileadjacent blocks 90B and 90C move in a nearly parallel manner. The figureillustrates that when moving in an antipodal manner, the blocks 90 donot obstruct each other's field of view 98. Yet, when moving in aparallel manner, or a near parallel manner, obstruction may occur.

A similar observation is made by FIG. 43C, wherein the adjacent blocks90B and 90C move in an antipodal manner, while the adjacent blocks 90Aand 90B move in a near parallel manner.

Again, it will be appreciated that many other arrangements are similarlypossible. For example, all the pairing combinations of the blocks 90 maymove in an antipodal manner, all the blocks 90 may move in parallel, orthe blocks 90 may move independently. It will be appreciated that an oddnumber of blocks 90 may be used in the assembly 92.

FIG. 43D illustrates possible dimensions for the cardiac model 250. Thedimensions are in mm It will be appreciated that other dimensions aresimilarly possible. Furthermore, It will be appreciated that the model250 may be based on general medical information of the organ 215 andcommon pathological features associated with it. Additionally, the modelmay be based on information related to a specific patient, such as age,sex, weight, and body type. Furthermore, a structural image, such as byultrasound or MRI, may be used for providing information about the sizeand location of the heart 215 in relation to the body section 230 (FIG.5A), for generating the model 250.

FIG. 43E schematically illustrates a possible arrangement of the blocks90 for viewing the volume U of the model 250, within the anatomicalconstrains AC. The significance of the present invention, as illustratedby FIG. 43E is that all the blocks maintain a close proximity to themodeled volume U, and to the region of interest, in vivo, even as theymove. This is in sharp contrast to the prior art, for example, as taughtby U.S. Pat. No. 6,597,940, to Bishop, et al, and U.S. Pat. No.6,671,541, to Bishop, in which the blocks are fixed within a rigidhousing, so that as some of the blocks are placed in close proximity tothe body, others are forced away from the body, and their countingefficiency deteriorates.

Preferably, the radiopharmaceuticals associated with the probe of FIGS.37A-52E may be Myoview™ (technetium Tc-99m tetrofosmin), a cardiacimaging agent, of GE Healthcare, GE Medical Systems,http://www.gehealthcare.com/contact/contact_details.html#diothers.Alternatively, it may be Cardiolite (Sestamibi radilabeled with TC99),of DuPont,http://www1.dupont.com/NASApp/dupontglobal/corp/index.jsp?page=/content/US/en_US/contactus.html.It will be appreciated that other agents may be used.

It will be appreciated that cardiac imaging, in accordance withembodiments of the present invention relates to the imaging of the wholeheart, or to a portion of the heart, or to blood vessels near the heart,for example, the coronary artery.

Example 13

Referring further to the drawings, FIG. 44 schematically illustrates adual imaging system 700 for radioactive-emission-measurements in tandemwith a three-dimensional structural imager, in accordance with apreferred embodiment of the present invention.

The dual imaging system 700 includes a three-dimensional structuralimager 720, preferably, on a structural-imager gantry 722, and aradioactive-emission measuring probe 730, preferably, on a probe gantry732. A patient 750 may lie on a bed 740, which is adapted for motioninto the radioactive-emission measuring probe 730 and thethree-dimensional structural imager 720, on a bed gantry 742.

A control unit 710 controls the operation of the dual system 700,including the three-dimensional structural imager 720, theradioactive-emission measuring probe 730, and the bed 740. The controlunit 710 may also analyze the data.

Alternatively, two control units may be used, one for controlling thethree-dimensional structural imager 720 and another for controlling theradioactive-emission measuring probe 730. It will be appreciated thatthe control system of the radioactive-emission measuring probe 730generally controls the order of the to operation of the dual system 700,wherein the radioactive-emission measuring may be performed before orafter the structural imaging.

It will be further appreciated that the radioactive-emission measuringprobe 730 may be configured as an add-on system, adapted for operatingwith an existing structural imager. It may be supplied with a dedicatedsoftware, for example, in a CD format, or with its own control unit,which is preferably adapted for communication with the structural imagercontrol unit.

The three-dimensional structural imager 720 may be, for example, a CT oran MRI, which defines a frame of reference, wherein theradioactive-emission measuring probe 730 is co-registered to the frameof reference.

In this manner, co-registration of functional and structural images ispossible. Additionally, the structural image may be used for providingtissue information for attenuation correction of the functional image,resulting in a more accurate functional image.

The radioactive-emission measuring probe 730 may be constructed as onearc 730A, preferably adapted for viewing a full width of a body from asingle position of the probe 730. Alternatively, theradioactive-emission measuring probe 730 may be constructed as two arcs730A and 730B, which are adapted for viewing a full circumference of abody, from a single position of the probe 730. It will be appreciatedthat the probe 730 may have other geometries, for example, a circle, anellipse, a polygon, a plurality of arcs forming a circle, or a pluralityof sections, forming a polygon, or other shapes.

Preferably, where the probe 730 is adapted for viewing a fullcircumference of a patient, from a single position, the bed 740 isformed as a stretcher, with a sheet 744, which is substantiallytransparent to radioactive emission, for example, of a hydrocarbonmaterial.

FIG. 45 schematically illustrates a cross-sectional view of dual imagingsystem 700 for radioactive-emission-measurements in tandem with athree-dimensional structural imager, in accordance with a preferredembodiment of the present invention.

Preferably, the gantry 732 of the probe 730 is adapted for verticalmotion, as described by the arrows 734, so as to bring the probe 730closer to the patient 750.

Additionally, the gantry 722 of the three-dimensional structural imager720 may be adapted for rotation, as described by an arrow 724.

The bed 740 is preferably adapted for motion into and out of the probe730 and the three-dimensional structural imager 720.

Preferably, the rate of imaging by the three-dimensional structuralimager 720 and by the radioactive-emission measuring probe issubstantially the same, to the bed moves into the two imagers at aconstant speed.

It will be appreciated that the body structure that may be imaged may bean organ, such as a heart or a pancreas, a gland, such as a thyroidgland or a lymph gland, blood vessels, for example, the coronary arteryor the pulmonary artery, a portion of an organ, such as an aorta or aleft atrium of a heart, a bone, a ligament, a joint, a section of thebody, such as a chest or an abdomen, or a whole body.

Preferably, the radiopharmaceuticals associated with the probe of thepresent invention be any one of the following:

1. anti-CEA, a monoclonal antibody fragment, which targets CEA—producedand shed by colorectal carcinoma cells—and may be labeled by Tc^(99m) orby other radioisotopes, for example, iodine isotopes (Jessup J M, 1998,Tumor markers—prognostic and therapeutic implications for colorectalcarcinoma, Surgical Oncology; 7: 139-151);

2. In¹¹¹-Satumomab Pendetide (Oncoscint®), designed to target TAG-72, amucin-like glycoprotein, expressed in human colorectal, gastric,ovarian, breast and lung cancers, but rarely in healthy human adulttissues (Molinolo A; Simpson J F; et al., 1990, Enhanced tumor bindingusing immunohistochemical analyses by second generationanti-tumor-associated glycoprotein 72 monoclonal antibodies versusmonoclonal antibody B72.3 in human tissue, Cancer Res., 50(4): 1291-8);

3. Lipid-Associated Sialic Acid (LASA), a tumor antigen, used forcolorectal carcinoma, with a similar sensitivity as anti-CEA monoclonalantibody fragment but a greater specificity for differentiating betweenbenign and malignant lesions (Ebril K M, Jones J D, Klee G G, 1985, Useand limitations of serum total and lipid-bound sialic acidconcentrations as markers for colorectal cancer, Cancer; 55:404-409);

4. Matrix Metaloproteinase-7 (MMP-7), a proteins enzyme, believed to beinvolved in tumor invasion and metastasis (Mori M, Barnard G F et al.,1995, Overexpression of matrix metalloproteinase-7 mRNA in human coloncarcinoma, Cancer; 75: 1516-1519);

5. Ga⁶⁷ citrate, used for detection of chronic inflammation (Mettler FA, and Guiberteau M J, Eds., 1998, Inflammation and infection imaging,Essentials of nuclear medicine, Fourth edition, Pgs: 387-403);

6. Nonspecific-polyclonal immunoglobulin G (IgG), which may be labeledwith both In¹¹¹ or Tc^(99m), and which has a potential to localizenonbacterial infections (Mettler F A, and Guiberteau M J, ibid);

7. Radio-labeled leukocytes, such as such as In¹¹¹ oxine leukocytes andTc^(99m) HMPAO leukocytes, which are attracted to sites of inflammation,where they are activated by local chemotactic factors and pass throughthe endothelium into the soft tissue (Mettler F A, and Guiberteau M J,ibid; Corstens F H; van der Meer J W, 1999, Nuclear medicine's role ininfection and inflammation, Lancet; 354 (9180): 765-70); and

8. Tc^(99m) bound to Sodium Pertechnetate, which is picked up by redblood cells, and may be used for identifying blood vessels and vitalorgans, such as the liver and the kidneys, in order to guide a surgicalinstrument without their penetration.

It will be appreciated that other agents may be used.

FIGS. 46A-46C schematically illustrate possible inner structures andarrangement of the probe 730, of the dual imaging system, in accordancewith preferred embodiments of the present invention.

FIG. 46A schematically illustrates the inner structure of the probe 730,showing the housing 20 and the parallel lines of the assemblies 92,possibly of an even number, each with the row of blocks 90, possiblyarranged in pairs. Each of the assemblies 92 preferably includes thededicated motion provider 76, for providing the rotational motion aroundx, and the dedicated secondary motion provider 78, for providing theoscillatory motion about r in the direction of the arrow 50.

The probe 730 defines an internal frame of reference 80, while eachassembly 92 has a reference cylindrical coordinate system of x;r, withrotation around x denoted by ω and rotation around r denoted by φ,wherein the oscillatory motion about r is denoted by the arrow 50.

Preferably, the motions of the assemblies 92 and the blocks 90correspond to those described hereinabove, in conjunction with FIGS.20A-20H and 22A-22H, as follows:

The plurality of blocks 90 is adapted for the windshield-wiper likeoscillatory motion, around the radius r, as denoted by the arrow 50. Theoscillatory motions may be synchronized in an antipodal manner, so as tobe diametrically opposed to each other, as shown hereinabove in FIGS.20B and 20E, by the arrows 54, and as shown hereinabove in FIGS. 20C and20F by the arrows 56. However, other motions are also possible. Forexample, the blocks 90 may move together, or independently. It will beappreciated that an odd number of blocks 90 is also possible.

Furthermore, the plurality of assemblies 92 are preferably arranged inparallel, and their rotational motions, around the x-axis, in thedirection of ω, may also be synchronized in an antipodal manner, so asto be diametrically opposed to each other, as shown hereinabove, in FIG.22C, by arrows 62, and as shown hereinabove in FIG. 22G, by arrows 64.However, other motions are also possible. For example, the assemblies 92may move together, or independently. It will be appreciated that an oddnumber of assemblies 92 is also possible.

Thus, the resultant traces are a large plurality of the broken linetraces 59, as seen hereinabove, in conjunction with FIGS. 22D and 22H,on the skin of the patient.

In accordance with the present example,

-   i. The different blocks 90 provide views from different    orientations;-   ii. The different blocks 90 change their view orientations;-   iii. The different assemblies 92 provide views from different    orientations; and-   iv. The different assemblies 92 change their view orientations.

The operational manner of the probe 730 is described hereinbelow inconjunction with FIG. 23D, for the at least two assemblies 92.

Preferably, the motions of the blocks 90 and of the assemblies 92 arecontained within the housing 20, so that the housing 20 of the probe 730remains stationary, wherein the external surface of the probe 730 issubstantially transparent to nuclear radiation. Alternatively, thehousing may be open on the side facing the patient.

It will be appreciated that the oscillatory motions need not besynchronized in an antipodal manner. Rather, the blocks 90 may movetogether, or independently. It will be appreciated that an odd number ofblocks 90 is also possible.

It will be appreciated that the probe 730 may include a plurality ofassemblies 92, which are not parallel to each other. For example, theassemblies 92 may be at right angles to each other, or at some otherangle. It will be appreciated that the assemblies 92 may includedetecting units 12 rather then blocks 90, for example, as in the probe10 of FIGS. 20A-20G.

FIG. 46B schematically illustrates a section 731 of the probe 730,showing the inner structure thereof, in accordance with anotherembodiment of the present invention. Accordingly, the probe 730 mayinclude the housing 20, and a single one of the assemblies 92, withinthe housing 20, having the dedicated motion provider 76, the dedicatedsecondary motion provider 78, and the rows of blocks 90. Additionally,in accordance with the present embodiment, the probe 730 includes atertiary motion provider 77, for sliding the assembly 90 laterally, inthe directions of an arrow 75.

FIG. 46C schematically illustrates an alternative arrangement of theblocks 90 around the volume U of the model 250, wherein each of theblocks 90 is provided with motion around the x axis, in the direction ofω, and with the oscillatory motion about r, preferably in the y-z plane,as illustrated by the arrow 50. Accordingly, the assemblies 92 need notbe used. Rather, each of the blocks 90 may communicate with two motionproviders which provide it with the two types of motion.

FIGS. 47A and 47B schematically illustrate the assembly 92 and the block90, in accordance with a preferred embodiment of the present invention.In essence, the assembly 92 is constructed in a manner similar to theprobe 10 of FIGS. 20A-20H, and specifically FIG. 20H, and according toFIG. 23D, hereinabove.

Thus the assembly 92 includes a row of at least two blocks 90, eachadapted of oscillatory motion about r. The blocks 90 are arranged withinthe inner housing 21.

A motor 88 and a shaft 85 form the motion provider 76, while a secondarymotor 86 and a secondary shaft 84 form the secondary motion provider 78,for the oscillatory motion about r. A plurality of motion transfersystems 74, for example gear systems, equal in number to the number ofblocks 90, transfer the motion of the secondary motion provider 78 tothe blocks 90. The motion transfer systems 74, of gears, make itpossible to provide the row of blocks 90 with any one of paralleloscillatory motion, antipodal oscillatory motion, or independent motion,depending on the gear systems associated with each block 90. It will beappreciated that other motion transfer systems, as known, may be used.

It will be appreciated that detecting units 12 may be used in place ofblocks 90.

In accordance with the present example, adjacent blocks 90A and 90B maymove in an antipodal manner and adjacent blocks 90C and 90D may move inan antipodal manner, while adjacent blocks 90B and 90C may move inparallel. It will be appreciated that many other arrangements aresimilarly possible. For example, all the pairing combinations of theblocks 90 may move in an antipodal manner, all the blocks 90 may move inparallel, or the blocks 90 may move independently. It will beappreciated that an odd number of blocks 90 may be used in the assembly92.

It will be appreciated that many other probes and probe systems may beconsidered and the examples here are provided merely to illustrate themany types of combinations that may be examined, in choosing and scoringa probe design, both in terms of information and in terms of secondaryconsiderations, such as rate of data collection, cost, and complexity ofthe design.

Example 14

Brain cancer is the leading cause of cancer-related death in patientsyounger than age 35, and in the United States, the annual incidence ofbrain cancer generally is 15-20 cases per 100,000 people.

There are two types of brain tumors: primary brain tumors that originatein the brain and metastatic (secondary) brain tumors that originate fromcancer cells that have migrated from other parts of the body.

Approximately 17,000 people in the United States are diagnosed withprimary cancer each year; nearly 13,000 die of the disease. Amongstchildren, the annual incidence of primary brain cancer is about 3 per100,000.

Primary Brain Tumors are generally named according to the type of cellsor the part of the brain in which they begin. The most common aregliomas, which begin in glial cells, and of which there are severaltypes, as follows:

Astrocytoma, a tumor which arises from star-shaped glial cells calledastrocytes, and which in adults, most often arises in the cerebrum,whereas in children, it occurs in the brain stem, the cerebrum, and thecerebellum.

Brain stem glioma, a tumor that occurs in the lowest part of the brain,and is diagnosed in young children as well as in middle-aged adults.

Ependymoma, a tumor, most common in middle-aged adults, which arisesfrom cells that line the ventricles or the central canal of the spinalcord and which occurs in children and young adults.

Oligodendroglioma, a rare tumor, which arises from cells that make thefatty substance that covers and protects nerves and usually occurs inthe cerebrum, grows slowly and generally does not spread intosurrounding brain tissue.

Some types of brain tumors do not begin in glial cells. The most commonof these are:

Medulloblastoma, also called a primitive neuroectodermal tumor, a tumorwhich usually arises in the cerebellum and is the most common braintumor in children.

Meningioma, which arises in the meninges and usually grows slowly.

Schwannoma, also called an acoustic neuroma, and occurring most often inadults, it is a tumor that arises from a Schwann cell, of the cells thatline the nerve that controls balance and hearing, in the inner ear.

Craniopharyngioma, a tumor which grows at the base of the brain, nearthe pituitary gland, and most often occurs in children.

Germ cell tumor of the brain, a tumor which arises from a germ cell,generally, in people younger than 30, the most common type of which is agerminoma.

Pineal region tumor, a rare brain tumor, which arises in or near thepineal gland, located between the cerebrum and the cerebellum.

Certain inherited diseases are associated with brain tumors, forexample, Multiple endocrine neoplasia type 1 (pituitary adenoma),Neurofibromatosis type 2 (brain and spinal cord tumors), Retinoblastoma(malignant retinal glioma), Tuberous sclerosis (primary brain tumors),and Von Hippel-Lindau disease (retinal tumor, CNS tumors). Furthermore,genetic mutations and deletions of tumor suppressor genes (i.e., genesthat suppress the development of malignant cells) increase the risk forsome types of brain cancer.

Additionally, exposure to vinyl chloride is an environmental risk factorfor brain cancer. Vinyl chloride is a carcinogen, used in themanufacturing of plastic products such as pipes, wire coatings,furniture, car parts, and house wares, and is present in tobacco smoke.Manufacturing and chemical plants may release vinyl chloride into theair or water, and it may leak into the environment as a result ofimproper disposal. People who work in these plants or live in closeproximity to them have an increased risk for brain cancer.

Secondary brain cancer occurs in 20-30% of patients with metastaticdisease and its incidence increases with age. In the United States,about 100,000 cases of secondary brain cancer are diagnosed each year.Patients with a history of melanoma, lung, breast, colon, or kidneycancer are at risk for secondary brain cancer.

Brain tumors can obstruct the flow of cerebrospinal fluid (CSF), whichresults in the accumulation of CSF (hydrocephalus) and increasedintracranial pressure (IICP). Nausea, vomiting, and headaches are commonsymptoms. They can damage vital neurological pathways and invade andcompress brain tissue. Symptoms usually develop over time and theircharacteristics depend on the location and size of the tumor.

The first step in diagnosing brain cancer involves evaluating symptomsand taking a medical history. If there is any indication that there maybe a brain tumor, various tests are done to confirm the diagnosis,including a complete neurological examination, imaging tests, andbiopsy.

Referring now to the drawings, FIGS. 48A-48B present the principles ofmodeling, for obtaining an optimal set of views, for a brain 215, inaccordance with embodiments of the present invention.

FIG. 48A schematically illustrates a body section 230, illustrating theorgan 215, being the brain 215. The brain 215 is enclosed within a skull830 and includes:

a cerebellum 802, which is the part of the brain below the back of thecerebrum. it regulates balance, posture, movement, and musclecoordination;

a corpus callosum 804, which is a large bundle of nerve fibers thatconnect the left and right cerebral hemispheres;

a frontal lobe of the cerebrum 806, which is the top, front regions ofeach of the cerebral hemispheres, and is used for reasoning, emotions,judgment, and voluntary movement;

a medulla oblongata 808, which is the lowest section of the brainstem(at the top end of the spinal cord) and controls automatic functionsincluding heartbeat, breathing, and the like;

a occipital lobe of the cerebrum 810, which is the region at the back ofeach cerebral hemisphere, at the back of the head, and contains thecenters of vision and reading ability;

a parietal lobe of the cerebrum 812, which is the middle lobe of eachcerebral hemisphere between the frontal and occipital lobes, located atthe upper rear of the head, and which contains important sensorycenters;

a pituitary gland 814, which is a gland attached to the base of thebrain that secretes hormones, and is located between the pons and thecorpus callosum;

pons 816, which is the part of the brainstem that joins the hemispheresof the cerebellum and connects the cerebrum with the cerebellum, locatedjust above the medulla oblongata;

a spinal cord 818, which is a thick bundle of nerve fibers that runsfrom the base of the brain to the hip area, through the spine(vertebrae);

a temporal lobe of the cerebrum 820, which is the region at the lowerside of each cerebral hemisphere, located at the sides of the head andcontaining centers of hearing and memory.

The brain 215 may include a pathological feature 213, termed herein anorgan target 213. A region of interest (ROI) 200 may be defined so as toencompass the brain 215 and the pathological feature 213.

As seen in FIG. 48B, the region of interest 200 of FIG. 48A is modeledas a model 250 of a volume U, and the organ target 213 is modeled as amodeled organ targets HS. Additionally, there are certain physicalviewing constraints, associated with the region of interest 200, whichare modeled as anatomical constraints AC. In the present case, the skull830 creates viewing constraints, and generally, imaging the brain isperformed extracorporeally.

Referring further to the drawings, FIG. 49 pictorially illustrates amethod 340 for zooming in on a suspected pathological feature, as aprocess of two or more iterations, in accordance with embodiments of thepresent invention, as follows:

As seen in FIG. 49, the method 340 may be described, pictorially, asfollows:

In I: The region of interest 200, associated with the organ 215, such asthe brain 215, is defined for the body section 230.

-   In II: The model 250 of the volume U is provided for the region of    interest 200, possibly with one or several of the modeled organ    targets HS, and within the anatomical constraints AC, for obtaining    the optimal set of views for the region of interest 200. The optimal    set of views is then applied to the region of interest 200,    encompassing the brain 215 of the body section 230.-   In III: When the suspected organ target 213 is identified, in vivo,    in the brain 215, by radioactive-emission measurements at the    optimal set of views, a second, inner region of interest 200′ is    defined, encircling the suspected pathological feature. For example,    if a suspected pathology 213 is identified in the occipital lobe 810    of the cerebrum, that is, the region at the back of each cerebral    hemisphere at the back of the head, the second region of interest    200′ is defined so as to encircle the occipital lobe 810 of the    cerebrum.-   In IV: A model 250′ of a volume U′ is provided for the second, inner    region of interest 200′, preferably, with at least one modeled organ    target HS, simulating the suspected organ target 213, for obtaining    an optimal pathology set of views for the region of interest 200′.    The second, pathology set of views is then applied to the second,    inner region of interest 200′ of the body section 230. In the    present example, the second, pathology set of views is then applied    to the occipital lobe 810 of the cerebrum, in vivo.

Referring further to the drawings, FIGS. 50A-51H schematicallyillustrate a probe system 850 for the brain, in accordance with apreferred embodiment of the present invention.

FIGS. 50A-50C schematically illustrate theradioactive-emission-measuring probe for the brain, in accordance withembodiments of the present invention;

Preferably, radioactive-emission-measuring probe 850 for the brain isshaped as a helmet 860, adapted for wearing on a head 862. The helmet860 is preferably mounted on a gantry 870, which may be adjustable inthe directions of arrows 872, 874 and 876, for adapting to individualheights and comfort.

Alternatively, no gantry is used, and the helmet 860 may be worndirectly on the head 862, for example, like a motorcycle helmet.

A chair 880 may be provided for the comfort of the patient.

Preferably, the radioactive-emission-measuring probe 850 for the brainis operable with a control unit 890, which may be a desktop computer, alaptop, or the to like. The control unit 890 is preferably used both forcontrolling the motions of the detecting units 12, blocks 90 andassemblies 92 of the radioactive-emission-measuring probe 850 for thebrain and for analyzing the data.

It will be appreciated that the radioactive-emission-measuring probe 850for the brain may be supplied merely as the probe helmet 860 and a datastorage device, such as a CD 892, a disk 892, or the like, containingthe appropriate software, for operation with an existing computer, atthe site.

It will be appreciated that the radioactive-emission-measuring probe 850for the brain may be operable with a structural imager, as taught bycommonly owned PCT publication WO2004/042546, whose disclosure isincorporated herein by reference. The structural imager may be ahandheld ultrasound imager, possibly with a position-tracking device, a3-D imager such as an ultrasound imager, a CT imager, or an MRI imager,as known. The data provided by the structural imager may be used for anyone or a combination of the following:

-   i. obtaining accurate dimensional data for modeling the brain 215,    as taught in conjunction with FIGS. -48A-49 and 11-12;-   ii. providing attenuation correction for the    radioactive-emission-measurements, based on the structural data, as    taught by commonly owned PCT publication WO2004/042546; and-   iii. co-registering the functional and structural images, as taught,    for example, by commonly owned PCT publication WO2004/042546.

Referring further to the drawings FIGS. 51A-51K schematically illustrateinner structures of the probe 850, for the brain, in accordance withseveral embodiments of the present invention.

FIG. 51A schematically illustrates the assembly 92, comprising, forexample four of the blocks 90, adapted for oscillatory motion about ther-axis, as illustrated by the arrows 50, and adapted for rotationalmotion about the x-axis, as illustrated by the arrow 62, as taught, forexample, in conjunction with FIGS. 22A-22H. It will be appreciated thatdetecting units 12 may be used in place of blocks 90.

FIG. 51B schematically illustrates a possible cross sectional view ofthe probe 850 (FIG. 50C), showing an arrangement of the assemblies 92,laterally around the head 862.

FIG. 51C schematically illustrates a top view of the probe 850, showingan arrangement of the assemblies 92, laterally around the head 862. Itwill be appreciated that the number of the blocks 90 may vary around thehead 862.

FIGS. 51D and 51E schematically illustrate other possible crosssectional views of the probe 850, showing arrangements of the assemblies92, vertically around the head 862.

FIG. 51F schematically illustrates the probe 850 formed as the helmet860, with the assemblies 92, arranged as illustrated by the crosssectional view of FIG. 51E. It will be appreciated that otherarrangements are similarly possible. Preferably, the probe helmet 860includes a housing 864. Preferably, the motions of the blocks 90 and ofthe assemblies 92 are contained within the housing 864.

Preferably, the proximal side of the housing 864 with respect to thehead 862 (FIG. 50C) is transparent to nuclear radiation. Alternatively,the proximal side with respect to the head 862 is open.

FIG. 51G schematically illustrates another arrangement of the blocks 90around the head 862, wherein the blocks 90 are not arranged inassemblies 92; rather each block 90 moves as an individual body. It willbe appreciated that the detecting units 12 may be used in place of theblocks 90.

FIGS. 51H-51K schematically illustrate possible rotational motions ofthe blocks 90, each of the blocks 90 moving as an individual body forobtaining views of different orientations. As seen in FIG. 51H, theblock 90 rotates around x as seen by an arrow 852 and at each positionaround x, oscillates about x, as seen by an arrow 851. The resultanttraces are seen in FIG. 51I as a star of line traces 854.

Alternatively, as seen in FIG. 51J, the block 90 rotates around y asseen by an arrow 853 and at each position around y, oscillates about x,as seen by the arrow 851. The resultant traces are seen in FIG. 51K, asline traces 855.

The assembly 92 and the block 90, in accordance with a preferredembodiment of the present invention are described in FIGS. 40A and 40B,hereinabove.

Thus the assembly 92 includes a row of at least two blocks 90, eachadapted of oscillatory motion about r. The blocks 90 are arranged withinthe inner housing 21.

A motor 88 and a shaft 85 form the motion provider 76, while a secondarymotor 86 and a secondary shaft 84 form the secondary motion provider 78,for the to oscillatory motion about r. A plurality of motion transfersystems 74, for example gear systems, equal in number to the number ofblocks 90, transfer the motion of the secondary motion provider 78 tothe blocks 90. The motion transfer systems 74, of gears, make itpossible to provide the row of blocks 90 with any one of paralleloscillatory motion, antipodal oscillatory motion, or independent motion,depending on the gear systems associated with each block 90. It will beappreciated that other motion transfer systems, as known, may be used.

It will be appreciated that detecting units 12 may be used in place ofblocks 90.

In accordance with the present example, adjacent blocks 90A and 90B maymove in an antipodal manner and adjacent blocks 90C and 90D may move inan antipodal manner, while adjacent blocks 90B and 90C may move inparallel. It will be appreciated that many other arrangements aresimilarly possible. For example, all the pairing combinations of theblocks 90 may move in an antipodal manner, all the blocks 90 may move inparallel, or the blocks 90 may move independently. It will beappreciated that an odd number of blocks 90 may be used in the assembly92.

It will be appreciated that imaging, in accordance with embodiments ofthe present invention relates to the imaging of the whole brain, or to aportion of the brain, or to blood vessels near the brain, for example,the coronary artery.

Preferably, the radiopharmaceuticals associated with the probe of thepresent invention may be Tc99m-d, 1-hexamethyl propylene amine oxime(1-HMPAO) commercially known as Ceretec by GE-Amersham, or ^(99m)Tc-ECD,commercially known as Neurolite, and made by Bristol Myers Squibb.

The present invention applies to the two types of brain tumors: primarybrain tumors, which originate in the brain and metastatic (secondary)brain tumors that originate from cancer cells that have migrated fromother parts of the body.

Additionally, the primary brain tumors may be gliomas, which begin inglial cells, and of which there are several types, as follows:

Astrocytoma, a tumor which arises from star-shaped glial cells calledastrocytes, and which in adults, most often arises in the cerebrum,whereas in children, it occurs in the brain stem, the cerebrum, and thecerebellum.

Brain stem glioma, a tumor that occurs in the lowest part of the brain,and is to diagnosed in young children as well as in middle-aged adults.

Ependymoma, a tumor, most common in middle-aged adults, which arisesfrom cells that line the ventricles or the central canal of the spinalcord and which occurs in children and young adults.

Oligodendroglioma, a rare tumor, which arises from cells that make thefatty substance that covers and protects nerves and usually occurs inthe cerebrum, grows slowly and generally does not spread intosurrounding brain tissue.

Additionally or alternatively, the present invention applies to othertypes of brain tumors, which do not begin in glial cells. The mostcommon of these are:

Medulloblastoma, also called a primitive neuroectodermal tumor, a tumorwhich usually arises in the cerebellum and is the most common braintumor in children.

Meningioma, which arises in the meninges and usually grows slowly.

Schwannoma, also called an acoustic neuroma, and occurring most often inadults, it is a tumor that arises from a Schwann cell, of the cells thatline the nerve that controls balance and hearing, in the inner ear.

Craniopharyngioma, a tumor which grows at the base of the brain, nearthe pituitary gland, and most often occurs in children.

Germ cell tumor of the brain, a tumor which arises from a germ cell,generally, in people younger than 30, the most common type of which is agerminoma.

Pineal region tumor, a rare brain tumor, which arises in or near thepineal gland, located between the cerebrum and the cerebellum.

Additionally or alternatively, the present invention applies to tumorsassociated with certain inherited diseases, for example, Multipleendocrine neoplasia type 1 (pituitary adenoma), Neurofibromatosis type 2(brain and spinal cord tumors), Retinoblastoma (malignant retinalglioma), Tuberous sclerosis (primary brain tumors), and VonHippel-Lindau disease (retinal tumor, CNS tumors), and genetic mutationsand deletions of tumor suppressor genes (i.e., genes that suppress thedevelopment of malignant cells), which increase the risk for some typesof brain cancer.

Additionally or alternatively, the present invention applies to tumorsassociated with exposure to vinyl chloride.

Additionally or alternatively, the present invention applies tosecondary brain cancer, for example, originating from the lungs, thebreasts, or other parts of the body.

It will be appreciated that the present invention further applies toother types brain tumors, which may be malignant or benign, blood clotsin the brain, and other brain pathologies. It will be appreciated thatmany other probes and probe systems may be considered and the exampleshere are provided merely to illustrate the many types of combinationsthat may be examined, in choosing and scoring a probe design, both interms of information and in terms of secondary considerations, such asrate of data collection, cost, and complexity of the design.

Example 15

FIG. 52A pictorially illustrates a method for zooming in on a suspectedpathological feature in a breast, as a process of two or moreiterations, in accordance with an embodiment of the present invention.

As seen in FIG. 52A, the method 340 may be described, pictorially, asfollows:

-   In I: The region of interest 200, associated with the organ 215,    such as the breast 215, is defined for the body section 230.-   In II: The model 250 of the volume U is provided for the region of    interest 200, possibly with one or several of the modeled organ    targets HS, and within the anatomical constraints AC, for obtaining    the optimal set of views for the region of interest 200. The optimal    set of views is then applied to the region of interest 200,    encompassing the breast 215 of the body section 230.-   In III: When the suspected organ target 213 is identified, in vivo,    in the breast 215, by radioactive-emission measurements at the    optimal set of views, a second, inner region of interest 200′ is    defined, encircling the suspected pathological feature.-   In IV: A second model 250′ of a second volume U′ is provided for the    second, inner region of interest 200′, preferably, with at least one    modeled organ target HS, simulating the suspected organ target 213,    for obtaining an optimal pathology set of views for the second    region of interest 200′. The second, pathology set of views is then    applied to the second, inner region of interest 200′ of the body    section 230.

Alternatively, FIG. 52B pictorially illustrates a method for zooming inon a suspected pathological feature in a breast, when the breast is heldbetween support and compression plates, as a process of two or moreiterations, in accordance with another embodiment of the presentinvention.

Thus, as seen in FIG. 52B, the method 340 may be described, pictorially,as follows:

-   In I: The region of interest 200, associated with the organ 215,    such as the breast 215, is defined for the body section 230, when    compressed between two plates 902 and 904, for example, mammograph    plates.-   In II: The model 250 of the volume U is provided for the region of    interest 200, possibly with one or several of the modeled organ    targets HS, and within the anatomical constraints AC, representing    the mammograph plates, for obtaining the optimal set of views for    the region of interest 200. The optimal set of views is then applied    to the region of interest 200, encompassing the breast 215 of the    body section 230.-   In III: When the suspected organ target 213 is identified, in vivo,    in the breast 215, by radioactive-emission measurements at the    optimal set of views, a second, inner region of interest 200′ is    defined, encircling the suspected organ target 213.-   In IV: A second model 250′ of a second volume U′ is provided for the    second, inner region of interest 200′, preferably, with at least one    modeled organ target HS, simulating the suspected organ target 213,    for obtaining an optimal pathology set of views for the second    region of interest 200′. The second, pathology set of views is then    applied to the second, inner region of interest 200′ of the body    section 230.

Mammography is currently the most effective method of screening forbreast cancer, for the detection of early non-palpable tumors. Inessence, it involves compressing the breast between two plates, asupport plate and a compression plate, and passing x-rays through thecompressed breast. The compression is desirous both in order to spreadthe breast fatty tissue thin, to reduce its attenuation, and in order tofix the breast tissue, with respect to a frame of reference, so that thex-ray image may be correlated with a surgical tool frame of reference,such as a biopsy needle frame of reference, for guiding the surgicaltool to a suspected location on the x-ray image, without the breasttissue moving between the taking of the x-ray image and the guiding ofthe surgical tool.

Often stereotactic mammography is applied, meaning that the x-ray headis rotated with respect to the plates, so as to provide at least twoviews of the fixed breast, compressed between the plates, from at leasttwo angles, for stereo imaging.

In general, each breast is imaged separately, generally, both in avertical direction and from the side (laterally), preferably,stereotactically. In other words, generally, at least four views of eachbreast are taken, two vertically and two laterally.

A surgical instrument, for example, a biopsy needle, or an ablationdevice, such as a cryosurgery device, an ultrasound ablation device, aknife, or a laser ablation device, may be built onto the mammograph, itsframe of reference correlated with that of the x-ray image.

FIG. 53A schematically illustrates the basic mammograph 900, showing astructural support 929, which defines a frame of reference 80, and whichincludes a support plate 902 and a compression plate 904, thecompression plate 904 being adapted for motion along an arrow 906, so asto compress a breast 909 on the support plate 902.

An x-ray tube 905 is preferably arranged so as to move within a track907, for obtaining x-ray images of the compressed breast 909 from atleast two views, so as to obtain stereotactic viewing, for depthevaluation. A film 901 is preferably arranged under the breast 909, forexample, under the support plate 902, for registering the x-ray image.

Additionally, the mammograph 900 is preferably adapted for rotation, asillustrated by an arrow 908, for compressing a breast from at least twoorientations, for example vertically and laterally.

A surgical tool 903, for example, a biopsy needle 903 or an ablationdevice 903, such as by cryosurgery or laser, or a knife 903, may bebuilt onto the mammograph 900, its frame of reference correlated withthe frame of reference 80, using position tracking devices or a linkagesystem, as known.

FIG. 53B schematically illustrates a system 925 of an ultrasound imager915, operative with the two plates 902 and 904, in accordance withembodiments of to the present invention. The importance of performingultrasound between two plates, as in the case of x-rays, is that the twoplates fix the breast with respect to the frame of reference 80, and infact, convert the breast to a rigid-like tissue, so that any suspiciousfindings can be located by the surgical tool 903.

In FIG. 53B, the ultrasound imager 915 is arranged to slide along tracks917, for example, on the compression plate 904, while a layer of gel 913or hydrogel 913, between the compression plate 904 and the breast 909ensures good contact for ultrasound imaging. In this manner, anultrasound image, correlated to the frame of reference 80, when thebreast is under compression, may be obtained.

FIG. 53C schematically illustrates a system 925 of an ultrasound imager915, operative with the two plates 902 and 904, and a surgicalinstrument, co-registered to the ultrasound imager, in accordance withembodiments of the present invention.

As seen in FIG. 53C the ultrasound imager 915 may be built onto thestructural support 929, its frame of reference correlated with the frameof reference 80, using position tracking devices or a linkage system, asknown.

Referring further to the drawings, FIGS. 54A-54E schematicallyillustrate an assembly, configured for operation with a mammoraph-likeradioactive-emission-measuring probe for the breast, in accordance withembodiments of the present invention

Specifically, FIG. 54A schematically illustrates an external appearanceof the radioactive-emission-measuring probe 1000, for the breast. Theprobe 1000 has a driving portion 990 and an imaging portion 980,enclosed in a sheath 985. The imaging portion 980 defines cylindricalcoordinates 987 of a longitudinal axis along the x-axis, and an r-axis,perpendicular to the longitudinal axis.

FIGS. 54B-54C schematically illustrate an internal structure of theradioactive-emission-measuring probe 1000, for the breast. The imagingportion 980 includes several of the blocks 90, for example, between twoand six of the blocks 90, arranged within the sheath 985. It will beappreciated that another number, which may be larger or smaller, andwhich may be odd or even, may be employed.

In FIG. 54C, the motions experienced by the blocks 90 are illustratedwith respect to the cylindrical coordinates 987 of x;r.

A first motion is a rotational motion of all the blocks 90, moving as asingle body, with the shaft 85 and the internal housing 21, around thex-axis, in the direction between +ω and −ω, as illustrated by the arrow52. The first motion is powered by the motor 88.

A second motion is an oscillatory motion of the individual blocks 90,powered by the secondary motor 86, the secondary shaft 84, and themotion transfer link 74, the motion transfer link 74 moving in a linear,sliding motion, as shown by the arrow 71.

At each orientation of the internal housing 21 with respect to ω, aroundx, the second, oscillatory motion about r takes place, individually byeach of the block 90, the oscillatory motion about r being between −φand +φ, as illustrated by the arrow 50, and as taught hereinabove, inconjunction with FIG. 21A-21H.

Thus, the overall motion is as illustrated hereinabove, in conjunctionwith FIG. 16D and FIGS. 21A-21H.

Further as seen in FIG. 54C, the rotational motion in the direction ofthe arrow 52 is provided by a motor 88 and the shaft 85, which togetherform the motion provider 76. The motor 88 may be an electric motor, forexample, a servo motor. The oscillatory motion in the direction of thearrow 50 is provided by a secondary motor 86, a secondary shaft 84 and amotion transfer link 74. The secondary motor 86 may also be an electricmotor, for example, a servo motor. The secondary motor 86, secondaryshaft 84 and the motion transfer link 74, together, form the secondarymotion provider 78, for the oscillatory motion, in the direction of thearrow 50.

Thus, for the radioactive-emission-measuring probe 1000, for the breast:

-   i. The different blocks 90 provide views from different    orientations; and-   ii. The different blocks 90 may change their view orientations    independent of each other.

It is important to point out that during the operation of the probe1000, the sheath 985 of the imaging portion 980 (FIGS. 54A and 54B)remains stationary, while the internal housing 21 (FIG. 54C) rotatesaround the x axis. The sheath 985 may be formed of a carbon fiber, aplastic, or another material, which is substantially transparent tonuclear radiation.

FIGS. 54D and 54E illustrate further the oscillatory motion of theblocks 90, within the sheath 985, as described by the arrows 50, byshowing the blocks 90 at different positions, along their oscillatorytravel. FIGS. 54D and 54E further illustrate a viewing side 986 and aback side 988 for the probe 1000.

Referring further to the drawings, FIGS. 55A-55K schematicallyillustrate systems 910, which include the radioactive-emission-measuringprobes 1000 for the breast, operating with systems, in which a breast iscompressed between two plates, to for example, as in the mammograph 900,in accordance with embodiments of the present invention.

Preferably, as seen in FIGS. 55A and 55B, the probes 1000 are mountedonto the two plates, the compression plate 904, and the support plate902, such that their viewing sides 986 face each other. Preferably, theprobes 1000 are aligned with the x axis, as seen. Alternatively, theprobes 1000 may be aligned with the y axis. It will be appreciated thatthe probes 1000 may be mounted only on one plate, the compression plate904 or the support plate 902.

Additionally, as seen in FIG. 55C, one or several of the probes 1000 maybe mounted as edge probes, for positioning at edges 992 and 994,supplementing the probes 1000 mounted on the plates, for obtaining viewsfrom the sides of the compressed breast.

An alternative embodiment is illustrated in FIG. 55D, wherein a singleone of the probes 1000 may be mounted on each of the plates 902 and 904,the probe 1000 being adapted for travel along a track 914, in adirection of an arrow 918, by a dedicated motion provider 916, thusproviding the views that a plurality of the probes 1000 would haveprovided, as illustrated in FIGS. 55A-55B.

It will be appreciated that edge probes 1000, may be added to theembodiment of FIG. 55D, in a manner similar to that of FIG. 55C.

FIG. 55E schematically illustrates a control unit 890, for controllingthe motions of the blocks 90 or the detecting units 12 (FIGS. 20A-22D)of the probes 1000 and for analyzing the measurements and constructingthe images. Preferably, a single control unit is used both for the x-rayimager, or the ultrasound imager 915, on the one hand, and theradioactive-emission-measuring probes 1000, on the other. Alternatively,individual control units may be used, one for each modality.Alternatively, the system 910 for the breast is provided with a storagedevice 892, such as a CD or a disk, which contains the software foroperating the system 910 for the breast with an existing computer on thesite. It will be appreciated that the control unit 890 may be a PC, alaptop, a palmtop, a computer station operating with a network, or anyother computer as known.

In accordance with embodiments of the present invention, frames may beprovided for mounting the radioactive-emission-measuring probes 1000 onthe plates 902 and 904.

As seen in FIG. 55F, a frame 912 may be provided for either the supportplate 902 or the compression plate 904, designed for accepting theprobes 1000 lengthwise, by inserting the probes 1000 in holes 926.

Alternatively, as seen in FIG. 55G, the frame 912 may be designed foraccepting the probes 1000 widthwise.

Additionally, as seen in FIG. 55H, a frame 922 is designed for acceptingthe probes 1000 widthwise or lengthwise, wherein the frame 922 furtherincludes an edge section 924, for supporting the edge probes of FIG.55C.

Furthermore, as seen in FIG. 551, two complementary frames may beprovided, one designed as the frame 922, for accepting the probes 1000lengthwise (or widthwise) along the plate and for accepting the edgeprobes, as illustrated in FIG. 55H, and the other, designed as the frame912, for accepting the probes 1000 lengthwise (or widthwise) along theplate.

As seen in FIG. 55J, a frame 923 may be designed for accepting a singleone of the probes 1000, lengthwise, adapted for sliding widthwise alongthe plate, in a channel 928, by the dedicated motion provider 916.Alternatively, the frame 923 may be designed for accepting the probe1000 widthwise, adapted for sliding lengthwise.

As seen in FIG. 55K, a frame 927 may be designed for accepting a singleone of the probes 1000, for example, lengthwise, adapted for slidingwidthwise along the plate, in a channel 928, by the dedicated motionprovider 916, wherein the frame 927 further includes the edge section924, for supporting the edge probe 1000 of FIG. 55C.

In accordance with embodiments of the present invention, nuclear imagingby radioactive-emission-measurements, co-registered with x-raymammography, may be obtained as follows:

-   step 1: the breast is compressed between the plates;-   step 2: an x-ray mammography is performed, as seen in FIG. 53A,    preferably from at least two orientations of the x-ray tube 905;-   step 3: the probes 1000 are mounted on the plates, and    radioactive-emission measurements are performed;-   step 4: where necessary, the surgical tool 903 may be employed,    while the breast is still compressed between the two plates.

It will be appreciated that steps 2 and 3 may be performed in any order.

Preferably, the images of the x-ray mammography and the nuclear imagingare co-registered and analyzed together.

However, it will be appreciated that only nuclear imaging byradioactive-emission measurements may be performed, without x-rayimaging.

Where ultrasound imaging co-registered with nuclear imaging byradioactive-emission-measurements is desired, a method applies, asfollows:

-   step 1: a hydrogel layer is placed between one of the plates, for    example, the compression plate 904 and the breast, or a gel is    spread over the breast, so as to serve as an ultrasound interface    between the plate and the breast;-   step 2: the breast is compressed between the plates;-   step 3: the probes 1000 are mounted on the plates, and    radioactive-emission measurements are performed;-   step 4: the probes 1000 are replaced by an ultrasound imager, for    example as illustrated in FIG. 53B or 53C, and ultrasound imaging is    performed;-   step 5: where necessary, the surgical tool 903 may be employed,    while the breast is still compressed between the two plates.

It will be appreciated that the steps 3 and 4 may be performed in anyorder.

Preferably, the images of the x-ray mammography and the nuclear imagingare co-registered and analyzed together.

Referring further to the drawings, FIGS. 56A-56C schematicallyillustrate a radioactive-emission-measuring probe 930, for imaging abreast under vacuum, in accordance with another preferred embodiment ofthe present invention.

As seen in FIG. 56A, the probe 930 includes a vacuum cup 934, shaped asa cone and connected to a vacuum system 932, for creating a vacuum in acavity 935 within. The vacuum in the cavity is used both to stretch thebreast so as to spread the fatty tissue thin and to fix the breasttissue with respect to a frame of reference, so a surgical device may beemployed, where needed, while the breast tissue remains fixed in place.

A vacuum ring 936, for example of natural or synthetic rubber, helpsmaintain the vacuum in the cup 934.

The vacuum cup 934 defines the frame of reference 80 and a plurality ofthe blocks 90 are arranged along the walls 938 of the suction cup 934,each adapted for at least one, and preferably two rotational motions,for example, as illustrated in conjunction with FIGS. 25A-25E and FIGS.25I-25J, or FIGS. 25F-25H, for imaging a breast in the cavity 935.Alternatively, the blocks 90 may be arranged in the assemblies 92, asillustrated in conjunction with FIGS. 24A-24H.

A surgical tool may be attached to the probe 930, and correlated to itsframe of reference, for example as taught in conjunction with FIG. 53B.

The motions of the blocks 90 are preferably automatic, controlled by thecontrol unit 890 (FIG. 55C).

Preferably, the inner walls 938 of the cup 934 are substantiallytransparent to radioactive emission.

FIG. 56B schematically illustrates an embodiment wherein a vacuumcylinder 934 is used in place of a conical cup, and the blocks 90 arearranged in assemblies 92, for example, as illustrated in conjunctionwith FIGS. 16E and 24A-24H.

FIG. 56C schematically illustrates an embodiment wherein the vacuumcylinder 934 is used, and a single one of the assemblies 92 is arrangedfor traveling around the cylinder 934, in the direction of an arrow 940,by a motion provider 942.

Referring further to the drawings, FIGS. 57A-57F schematicallyillustrate a radioactive-emission-measuring probe 950, for imaging thebreasts in the natural state, in accordance with another preferredembodiment of the present invention.

As seen in FIG. 57A, the radioactive-emission-measuring probe 950, forimaging the breasts in a natural state, is designed as an extracorporealunit which may be positioned against the breasts, operating as taught inconjunction with any one of FIGS. 20A-25J. Preferably, theradioactive-emission-measuring probe 950, for imaging the breasts isattached to a gantry 952, which may provide adjustments as seen byarrows 954 and 956.

Additionally, the patient may be positioned on a chair 960, as seen inFIG. 57B.

The control unit 890 is illustrated in FIG. 57C.

The control unit 890 may be used for controlling the motions of theblocks 90 (FIGS. 24A-24H or 25A-25J) or the detecting units 12 (FIGS.20A-20G, or FIGS. 22A-22D) and for analyzing the measurements andconstructing the images. Alternatively, theradioactive-emission-measuring probe 910 for the breast is supplied witha storage device 892, which contains the software for operating theradioactive-emission-measuring probe 910 for the breast with an existingcomputer on the site. It will be appreciated that the control unit 890may be a PC, a laptop, a palmtop, a computer station operating with anetwork, or any other computer as known.

FIG. 57D schematically illustrates a woman 970 being examined by theradioactive-emission-measuring probe 950, when seated on the chair 960.It will be appreciated that the examination may also be conducted whenthe woman 970 is standing or lying on a bed.

FIG. 57E schematically illustrates the inner structureradioactive-emission-measuring probe 950 in accordance with a preferredembodiment of the present invention. FIG. 57E shows the housing 20, theparallel lines of assemblies 92, possibly of an even number, each with adedicated motion provider 76 and a dedicated secondary motion provider78, and the rows of blocks 90, possibly arranged in pairs, along theassemblies 92.

The probe 950 defines the frame of reference 80, while each assembly 92has a reference cylindrical coordinate system of x;r, with rotationaround x denoted by the arrow 62 and oscillatory motion about r, denotedby the arrow 50.

FIG. 57F schematically illustrates the model 250 of the two breasts,modeled as the volumes U, and the anatomical constraints associated withthem, for determining an optimal set of views for radioactive-emissionmeasurements.

It will be appreciated that imaging, in accordance with embodiments ofthe present invention relates to the imaging of the whole breast, or toa portion of the breast, the armpits near the breasts, (and) or the twobreasts.

Preferably, the radiopharmaceuticals associated with theradioactive-emission-measuring probe for the breast may be Tc^(99m)bound to Sestamibi, a small protein molecule, made for example, byBristol Myers Squibb, and marketed as Miraluma, used widely for breastcancer detection.

The present invention applies to detecting and differentiating betweenvarious types of breast disorders, for example as illustrated in FIG.1A, hereinabove, as follows.

i. fibroadenomas 8, which are fibrous, benign growths in breast tissue.

ii. cysts 9, which are fluid-filled sacs and may disappear sometimes bythemselves, or a doctor may draw out the fluid with a needle.

iii. a breast abscess 11, which is a collection of pus, resulting froman infection.

iv. fibrocystic breast disease 13, which is a common conditioncharacterized by an increase in the fibrous and glandular tissues in thebreasts, resulting in small, nodular cysts, noncancerous lumpiness, andtenderness, wherein treatment of the cysts may be all that is needed.

v. a tumor 15, which may be precancerous or cancerous, and which usuallyshows up as a white area on a mammogram even before it can be felt. Incases where the tumor 15 is cancerous, it may appear as a white areawith radiating arms. A cancerous tumor 15 may have no symptoms or maycause swelling, tenderness, discharge from the nipple 4, indentation ofthe nipple 4, or a dimpled appearance 17 in the skin over the tumor.

Additionally, the present invention applies to detecting various typesof breast cancers, such as:

i. ductal cancer, which affects the cells of the ducts;

ii. lobular cancer, which begins in the lobes or lobules of the breast;and

iii. inflammatory breast cancer, which is an uncommon type of breastcancer and causes the breast to be warm, red, and swollen.

It will be appreciated that the present invention further applies toother types breast disorders, which may be cancerous, precancerous, orbenign.

Additionally or alternatively, the present invention applies tosecondary breast cancer, for example, originating from the lungs, orother parts of the body.

Furthermore, the radioactive-emission-measuring probe for the breast maybe to designed for and used on a single breast or designed for and usedsimultaneously on the two breasts.

It will be appreciated that although breast cancer in men and childrenis rare, the present invention may be used for the detection of breastcancer in men and children as well.

It will be appreciated that many other probes and probe systems may beconsidered and the examples here are provided merely to illustrate themany types of combinations that may be examined, in choosing and scoringa probe design, both in terms of information and in terms of secondaryconsiderations, such as rate of data collection, cost, and complexity ofthe design.

It will be appreciated that the methods of the present invention applyto pathological features that may be modeled as regions of concentratedradiations, or hot regions, regions of low-level radiation, which isnonetheless above background level, and regions of little radiation, orcold regions, below the background level. However, in general, foridentifying a pathological feature of the heart, they relate to coldregions.

It will be appreciated that the methods of the present inventions may beoperable by computer systems and stored as computer programs oncomputer-readable storage media.

It will be appreciated that the body may be an animal body or a humanbody.

It will be appreciated that the radioactive-emission-measuring systems,probes and methods of the present invention may be used with commonlyowned US Applications 20040015075 and 20040054248 and commonly owned PCTpublication WO2004/042546, all of whose disclosures are incorporatedherein by reference. These describe systems and methods for scanning aradioactive-emission source with a radioactive-emission-measuring probeof a wide-aperture collimator, and at the same time, monitoring theposition of the radioactive-emission-measuring probe, at very fine timeintervals, to obtain the equivalence of fine-aperture collimation. Inconsequence, high-efficiency, high-resolution, images of aradioactive-emission source are obtained.

Commonly owned US application 20040054248 and commonly owned PCTpublication WO2004/042546 further disclose various extracorporeal andintracorporeal systems, of radioactive-emission-measuring probes, ofrelatively wide apertures, associated with position-tracking devices.

It will be appreciated that the radioactive-emission-measuring systems,probes and methods of the present invention may be used with commonlyowned U.S. Pat. No. 6,173,201 to Front, whose disclosure is incorporatedherein by reference, as well as by M. W. Vannier and D. E. Gayou,“Automated registration of multimodality images”, Radiology, vol. 169pp. 860-861 (1988); J. A. Correia, “Registration of nuclear medicineimages, J. Nucl. Med., vol. 31 pp. 1227-1229 (1990); J-C Liehn, A.Loboguerrero, C. Perault and L. Demange, “superposition of computedtomography and single photon emission tomography immunoscinigraphicimages in the pelvis: validation in patients with colorectal or ovariancarcinoma recurrence”, Eur. J. Nucl. Med., vol. 19 pp. 186-194 (1992);F. Thomas et al., “Description of a prototype emission transmissioncomputed tomography imaging system”, J. Nucl. Med., vol. 33 pp.1881-1887 (1992); D. A. Weber and M. Ivanovic, “Correlative imageregistration”, Sem. Nucl. Med., vol. 24 pp. 311-323 (1994); and Hasegawaet al., U.S. Pat. No. 5,376,795.

These relate to the acquisition of both a functional image of the body,such as a radioactive-emission image, and a structural image, such as anultrasound, an x-ray, or an MRI image, and their co-registration on asingle frame of reference.

In essence, several images may be acquired and co-registered to the sameframe of reference, as follows:

-   i. a first functional image scan, based for example, on anti-CEA    monoclonal antibody fragment, labeled by iodine isotopes, may be    acquired for targeting CEA—produced and shed by colorectal carcinoma    cells for detecting a pathological feature, such as colorectal    carcinoma;-   ii. a second functional image, based for example, on    nonspecific-polyclonal immunoglobulin G (IgG), which may be labeled    with Tc^(99m), may be acquired for locating blood vessels and vital    structures, such as the heart, or the stomach, co-registered with    the first functional image and the pathological feature detected on    it, in order to locate the pathological feature in reference to    blood vessels and vital organs; and-   iii. a structural image, such as an ultrasound image, may be used    for general structural anatomy, co-registered with the first and    second functional images, in order to locate the pathological    feature in reference to bones and the general anatomic structure.

Thus, a physician may locate the pathological feature in reference tothe blood vessels, vital organs, and the bones, and guide a minimallyinvasive surgical instrument to the pathological feature, while avoidingthe blood vessels, vital organs, and bones. The minimally invasivesurgical instrument may be a biopsy needle, a wire, for hot resection, aknife for cold resection, an instrument of focused energy, to produceablation, for example, by ultrasound, or by laser, an instrument forcryosurgery, an instrument for croyetherapy, or an instrument forbractherapy, wherein seeds of a radioactive metal are planted close to atumor, for operating as a radioactive source near the tumor.

Commonly owned PCT publication WO2004/042546 further discloses that thesurgical instrument may be visible on at least one of the images, forexample, on the structural image, to enable the physician to see theinstrument, the pathological feature, and the surrounding anatomy on thedisplay 129 (FIG. 3A). Additionally, the surgical instrument may beradioactively labeled, to be visible also on the functional image. PCTpublication WO2004/042546 further disclose various extracorporeal andintracorporeal systems, of radioactive-emission-measuring probes, andstructural imagers such as an ultrasound probe or an MRI probe.

Commonly owned U.S. Pat. No. 6,173,201, to Front further discloses amethod of stereotactic therapy, wherein a frame, which includes at leastthree markers, visible on a structural image, is rigidly secured to apatient. The structural image of a region inside the patient's body,which includes a pathological feature and the markers, is acquired. Afunctional image of the pathological feature is then acquired andco-registered with the structural image, to correlate the images to thesame frame of reference. A stereotactic guide is rigidly attached to theframe and is used to guide a surgical instrument, such as a biopsyneedle or a brachytherapy needle, to the pathological feature, withreference to the co-registered images.

Thus the radioactive-emission-measuring systems, probes and methods ofthe present invention may be used together with position trackingdevices, for enhanced image acquisition, they may be used together withstructural imager and structural imaging for correlating functional andstructural images, and they may be used for guiding minimally invasivesurgical instruments, such as a biopsy needle, a wire, for hotresection, a knife for cold resection, an instrument of focused energy,to produce ablation, for example, by ultrasound, or by laser, aninstrument for cryosurgery, an instrument for croyetherapy, or aninstrument for bractherapy.

It will be appreciated that a structural image, such as by ultrasoundmay further be used and in order to provide information about the sizeand location of the body structure 215 for the purpose of creating themodel 250 (FIG. 5A).

It will be appreciated that a structural image, such as by ultrasoundmay further be used and in order to provide information about tissueattenuation, for example, as taught in conjunction by commonly owned PCTpublication WO2004/042546, whose disclosure is incorporated herein byreference. The information may then be used to correct theradioactive-emission measurements.

It is expected that during the life of this patent many relevantradioactive-emission-measuring systems, probes and methods will bedeveloped and the scope of these terms is intended to include all suchnew technologies a priori.

As used herein the term “about” refers to ±20%.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad toscope of the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, any citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention.

What is claimed is:
 1. A camera for imaging of radiation emitted from a patient that includes:at least one assembly, the assembly comprises plurality of heads, each comprising at least one pixilated solid-state detector being configured to detect photons emitted from the body during image acquisition and being collimated to define one or more collection angles for the detector pixels; and one or more actuators which control the position and orientation of at least one of the heads relative to the assembly during image acquisition, wherein at least one of the heads is configured to be translated forward, relative to said assembly, along a general direction that the head is aimed at during image acquisition and to change its viewing direction by rotation while in a forward translated position.
 2. A camera according to claim 1, comprising a data processor which collects data acquired by said heads and reconstruct a 3D SPECT image therefrom.
 3. A camera according to claim 1, wherein a plurality of said heads are translatable and wherein directions of translation are different for different heads.
 4. A camera according to claim 3, wherein said heads are aimed in different directions during said translation in different directions.
 5. A camera according to claim 1, wherein a plurality of said heads are configured to move in a windshield wiper motion.
 6. A camera according to claim 1, configured for cardiac imaging.
 7. A camera according to claim 1, configured for bringing into proximity with body tissue to be imaged.
 8. A camera according to claim 1, configured for insertion into a body.
 9. A camera according to claim 1, comprising at least one position tracking device which tracks a position of said assembly.
 10. A camera according to claim 1, comprising a controller which activates said one or more actuators to move said one or more heads during data acquisition from said heads.
 11. A camera according to claim 1, comprising at least one actuator which moves a plurality of said heads in a lateral direction relative to a direction of view thereof.
 12. A camera according to claim 1, wherein said forward direction is away from a base portion of said assembly, relative to which base portion a plurality of said heads move.
 13. A camera according to claim 1, wherein at least two of said heads do not move synchronously.
 14. A camera according to claim 1, wherein at least two of said heads are aimable by said actuators at a same region of interest.
 15. A camera according to claim 1, wherein at least two of said heads are do not change a distance between them when translated.
 16. A camera according to claim 1, wherein at least two of said heads are configured to scan in a same plane.
 17. A camera according to claim 1, wherein at least two of said heads are configured to scan in different plane.
 18. A camera according to claim 1, wherein adjacent heads are configured to scan without touching each other.
 19. A method of radioimaging, comprising: (a) aiming a camera including a controller and a plurality of pixilated and collimated solid-state detector heads at a body location; (b) detecting photons emitted by said body, using said plurality of heads; (c) moving at least one of said heads during said detecting in a forward direction of a viewing by said head, under the control of said controller; (d) moving, during said detecting when said at least one head is in said forward direction, said at least one head in an angular motion relative to said forward direction, under the control of said controller; and (e) reconstructing a 3D SPECT image from said detected photons.
 20. A method according to claim 19, wherein said forward movement comprises movement towards a tissue of interest.
 21. A method according to claim 19, comprising selecting views according to a rotational ability of said heads, to cover a region of interest.
 22. A method according to claim 19, comprising selecting views according to a rotational ability of said heads, to cover a region of interest.
 23. A method according to claim 19, comprising moving a plurality of said plurality of heads towards a region of interest.
 24. A method according to claim 19, comprising moving said plurality of heads to scan a region of interest. 